Portable ultrasound device

ABSTRACT

Systems and methods for stroke detection in accordance with embodiments of the invention are illustrated. One embodiment includes a system for detecting strokes, including a processor, a first ultrasound transmitter located on a patient&#39;s head in communication with the processor, a first ultrasound receiver located on the patient&#39;s head in communication with the processor, a memory in communication with the processor, including a stroke diagnostics application, where the stroke diagnostics application directs the processor to transmit a first ultrasound signal from the first ultrasound transmitter across a patient&#39;s brain, the brain comprising a first and second hemisphere, receive the first ultrasound signal using the first ultrasound receiver, where the ultrasound signal is affected during transit by harmonics generated by microbubbles in the blood of the patient stimulated by the first ultrasound signal, and detect that a stroke has occurred based on the harmonic effects on the first received ultrasound signal.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. Non-Provisionalapplication Ser. No. 15/934,921 filed Mar. 23, 2018, which claims thebenefit of U.S. Provisional Application No. 62/476,638 filed Mar. 24,2017, the entirety of which is hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates generally to ultrasound diagnostictechnology, and more specifically to apparatuses and methods fordetecting internal injury using ultrasound.

BACKGROUND

Ultrasound waves are often described as sound waves having frequenciesgreater than 20 kHz. Ultrasound has been used in the medical field toobserve the interior of the human body in a non-invasive manner. Theultrasound is applied using an ultrasound transducer that typicallycomes into contact with the patient's skin. Ultrasound is readilyabsorbed in air, so gel is often used between the transducer and theskin to enhance the transmission of ultrasound. In some cases, the gelis a liquid substance. In other cases, a gel pad is used where the gelis molded into semi-solid disks.

A gel is a solid jelly-like material that can have properties rangingfrom soft and weak to hard and tough. Gels are defined as asubstantially dilute cross-linked system, which exhibits no flow when inthe steady-state. By weight, gels are mostly liquid, yet they behavelike solids due to a three-dimensional cross-linked network within theliquid. It is the crosslinking within the fluid that gives a gel itsstructure (hardness) and contributes to the adhesive stick (tack). Inthis way gels are a dispersion of molecules of a liquid within a solidin which the solid is the continuous phase and the liquid is thediscontinuous phase.

Microbubbles are bubbles that have a diameter on the micrometer scale,but smaller than one millimeter. Microbubbles can be used as ultrasoundcontrasting agents because they can oscillate and vibrate when a sonicenergy field is applied and may reflect ultrasound waves. Thisdistinguishes the microbubbles from surrounding tissues.

Strokes are a common cause of death in the United States of America.Every year, more than 795,000 people in the United States have a stroke.Strokes can be classified into two major categories: ischemic andhemorrhagic. Ischemic strokes are caused by the interruption of theblood supply to the brain, while hemorrhagic strokes result from therupture of a blood vessel or an abnormal vascular structure.

SUMMARY OF THE INVENTION

Systems and methods for stroke detection in accordance with embodimentsof the invention are illustrated. One embodiment includes A system fordetecting strokes, including a processor, a first ultrasound transmitterlocated on a patient's head in communication with the processor, a firstultrasound receiver located on the patient's head in communication withthe processor, a memory in communication with the processor, including astroke diagnostics application, where the stroke diagnostics applicationdirects the processor to transmit a first ultrasound signal from thefirst ultrasound transmitter across a patient's brain, the braincomprising a first hemisphere and a second hemisphere, receive the firstultrasound signal using the first ultrasound receiver, where theultrasound signal is affected during transit by harmonics generated bymicrobubbles in the blood of the patient stimulated by the firstultrasound signal, and detect that a stroke has occurred based on theharmonic effects on the first received ultrasound signal.

In another embodiment, the stroke diagnostics application furtherdirects the processor to compare the portion of the received ultrasoundsignal corresponding to the first hemisphere of the brain to the portionof the ultrasound signal corresponding to the second hemisphere of thebrain, and detect differences in microbubble signal profile between thefirst hemisphere and the second hemisphere based on the harmonic effectson the first received ultrasound signal.

In a further embodiment, the first ultrasound receiver is located on thepatient's head ipsilaterally with respect to the first ultrasoundtransmitter, and wherein the stroke diagnostics application furtherdirects the processor to transmit a second ultrasound signal from asecond ultrasound transmitter across the patient's brain, where thesecond ultrasound transducer is in communication with the processor andis located contralaterally on the patient's head with respect to thefirst ultrasound transmitter, and receive the second ultrasound signalusing a second ultrasound receiver, where the second ultrasound receiveris located ipsilaterally on the patient's head with respect to thesecond ultrasound transmitter, where the second ultrasound receiver isin communication with the processor, and where the second ultrasoundsignal is affected during transit by harmonics generated by microbubblesin the blood of the patient stimulated by the second ultrasound signal.

In still another embodiment, the stroke diagnostics application furtherdirects the processor to determine the transmit time of ultrasoundacross the patient's head, time-box the first received ultrasound signalsuch that the first time-boxed signal corresponds to the signal receivedduring a time period of half of the determined transmit time so that thefirst time-boxed signal describes the first hemisphere of the brain,time-box the second received ultrasound signal such that the secondtime-boxed signal corresponds to the signal received during a timeperiod of half of the determined transmit time so that the secondtime-boxed signal describes the second hemisphere of the brain, andcompare the first time-boxed signal and the second time-boxed signal fordifferences in harmonic responses.

In a still further embodiment, the first ultrasound is locatedcontralaterally on the patient's head with respect to the firstultrasound transmitter, and wherein the stroke diagnostics applicationfurther directs the processor to transmit a second ultrasound signalfrom the second ultrasound transmitter across the patient's brain, wherethe second ultrasound transmitter is located contralaterally on thepatient's head with respect to the first ultrasound transmitter, andreceive the second ultrasound signal using a second ultrasound receiver,where the second ultrasound receiver is located contralaterally on thepatient's head with respect to the first ultrasound transmitter, wherethe second ultrasound receiver is in communication with the processor,and where the second ultrasound signal is affected during transit byharmonics generated by microbubbles in the blood of the patientstimulated by the second ultrasound signal.

In yet another embodiment, the stroke diagnostics application furtherdirects the processor to locate the position of the detected strokewithin the brain.

In a yet further embodiment, the stroke diagnostics application furtherdirects the processor to time-box the received ultrasound signal toreflect spatial segments of the brain, and determine which spatialsegment contains harmonic effects indicating injury.

In another additional embodiment, the stroke diagnostics applicationfurther directs the processor to analyze a first segment of the receivedultrasound signal corresponding to the distance from the firstultrasound transmitter to a predetermined segment distance from thefirst ultrasound transmitter, and analyze a set of subsequent segments,where each subsequent segment in the set of subsequent segmentssequentially describes the received ultrasound signal from the firstultrasound transmitter to a distance that is one more predeterminedsegment distance away from the first ultrasound transmitter than theprevious segment.

In a further additional embodiment, the stroke diagnostics applicationfurther directs the processor to analyze a first segment of the receivedultrasound signal corresponding to the distance from the firstultrasound transmitter to a predetermined segment distance from the ofthe first ultrasound transmitter, and analyze a set of subsequentsegments, where each subsequent segment in the set of subsequentsegments sequentially describes the received ultrasound signal from theprevious segment to a distance that is one more predetermined segmentdistance away from the first ultrasound transmitter than the previoussegment.

In another embodiment again, the stroke diagnostics application furtherdirects the processor to determine whether the stroke is an ischemicstroke or a hemorrhagic stroke based on the received ultrasound signal.

In a further embodiment again, the stroke diagnostics applicationfurther directs the processor to match the harmonic effects to a knownset of harmonic effects stored in the memory.

In still yet another embodiment, the stroke diagnostics applicationfurther directs the processor to identify blood pooling by locatingharmonic effects representing microbubbles pooling in a region of thebrain for an extended period.

In a still yet further embodiment, the stroke diagnostics applicationfurther directs the processor to identify areas where no harmoniceffects representing microbubbles are present.

In still another additional embodiment, the microbubbles generatedifferent harmonic frequencies depending on the pressure that themicrobubbles are subject to, and wherein the stroke diagnosticsapplication further directs the processor to measure the frequenciesassociated with the microbubble harmonic effects, and calculate anintracranial pressure of the patient based on the measured frequencies,determine a type of stroke based on the intracranial pressure.

In a still further additional embodiment, the received first ultrasoundsignal is further affected by unwanted harmonic noise, and the strokedetection application further directs the processor to reduce unwantedharmonic noise by transmitting a second ultrasound signal using thefirst ultrasound transmitter, where the second ultrasound signal is 180degrees out of phase with the first transmitted ultrasound signal, andfilter the first ultrasound signal to remove unwanted harmonic noise,where the unwanted harmonic noise is correlated to phase.

In still another embodiment again, the received first ultrasound signalincludes a first peak and a second peak, where the received firstultrasound signal's first peak and second peak correspond to harmoniceffects, and wherein the stroke detection application further directsthe processor to locate the first received ultrasound signal's firstpeak by finding a first inflection point in the received firstultrasound signal, locate the first received ultrasound signal's secondpeak by finding a second inflection point in the received firstultrasound signal, and match the pattern of the peaks in the firstreceived ultrasound signal to predetermined patterns of peaksrepresenting brains suffering from stroke.

In a still further embodiment again, the stroke detection applicationfurther directs the processor to transmit a second ultrasound signalusing a second ultrasound transmitter, where the second ultrasoundtransmitter is located on the patient's head contralaterally withrespect to the first ultrasound transmitter, and where the secondultrasound transmitter is in communication with the processor, receivethe second ultrasound signal using at least one of the first ultrasoundreceiver and a second ultrasound receiver, where the second ultrasoundreceiver is located on the patient's head contralaterally with respectto the first ultrasound receiver, where the second received ultrasoundsignal comprises a first peak and a second peak, and where the secondultrasound signal's first peak and second peak correspond to harmoniceffects, locate the second received ultrasound signal's first peak byfinding a first inflection point in the received first ultrasoundsignal, locate the second received ultrasound signal's second peak byfinding a second inflection point in the received first ultrasoundsignal, calculate the differences between the first received ultrasoundsignal's peaks with the second received ultrasound signal's peaks, anddetect if a stroke has occurred based on the calculated differences.

In yet another additional embodiment, a first ultrasound transducerassembly comprises the first ultrasound transmitter and the firstultrasound receiver.

In a yet further additional embodiment, the first ultrasound transducerassembly comprises a coaxial dual element ultrasound transducer.

In yet another embodiment again, a method for detecting strokes includestransmitting a first ultrasound signal from a first ultrasoundtransmitter across a patient's brain, where the brain comprises a firsthemisphere and a second hemisphere, and receiving the first ultrasoundsignal using a first ultrasound receiver, where the ultrasound signal isaffected during transit by harmonics generated by microbubbles in theblood of the patient stimulated by the first ultrasound signal, anddetecting that a stroke has occurred based on the harmonic effects onthe first received ultrasound signal.

In a yet further embodiment again, detecting if a stroke has occurredfurther includes comparing the portion of the received ultrasound signalcorresponding to the first hemisphere of the brain to the portion of theultrasound signal corresponding to the second hemisphere of the brain,and detecting differences in microbubble signal profile between thefirst hemisphere and the second hemisphere based on the harmonic effectson the first received ultrasound signal.

In another additional embodiment again, the first ultrasound receiver islocated on the patient's head ipsilaterally with respect to the firstultrasound transmitter, and further includes transmitting a secondultrasound signal using a second ultrasound transmitter across thepatient's brain, where the second ultrasound transmitter is located onthe patient's head contralaterally with respect to the first ultrasoundtransmitter, and receiving the second ultrasound signal using a secondultrasound receiver, where the second ultrasound receiver is located onthe patient's head contralaterally with respect to the first ultrasoundtransmitter, and where the second ultrasound signal is affected duringtransit by harmonics generated by microbubbles in the blood of thepatient stimulated by the second ultrasound signal, and detecting if astroke has occurred is further based on the harmonic effects on thesecond received ultrasound signal.

In a further additional embodiment again, the method further includesdetermining the transit time of ultrasound across the patient's head,time-boxing the first received ultrasound signal such that the firsttime-boxed signal corresponds to the signal received during a timeperiod of half of the determined transmit time so that the firsttime-boxed signal describes the first hemisphere of the brain,time-boxing the second received ultrasound signal such that the secondtime-boxed signal corresponds to the signal received during a timeperiod of half of the determined transmit time so that the secondtime-boxed signal describes the second hemisphere of the brain, andcomparing the first time-boxed signal and the second time-boxed signalfor differences in harmonic responses.

In still yet another additional embodiment, the first ultrasoundreceiver is located on the patient's head contralaterally with respectto the first ultrasound transmitter, and the method further includestransmitting a second ultrasound signal from a second ultrasoundtransmitter across the patient's brain, where the second ultrasoundtransmitter is located on the patient's head contralaterally withrespect to the first ultrasound transmitter, receiving the secondultrasound signal using a second ultrasound receiver, where the secondultrasound receiver is located on the patient's head ipsilaterally withrespect to the first ultrasound transmitter, and where the secondultrasound signal is affected during transit by harmonics generated bymicrobubbles in the blood of the patient stimulated by the secondultrasound signal, and detecting if a stroke has occurred is furtherbased on the harmonic effects on the second received ultrasound signal.

In another embodiment, the method further includes locating the positionof the detected stroke within the brain.

In a further embodiment, locating the position of the detected strokewithin the brain includes time-boxing the received ultrasound signal toreflect spatial segments of the brain, and determining which spatialsegment contains harmonic effects indicating injury.

In still another embodiment, time-boxing the received ultrasound signalincludes analyzing a first segment of the received ultrasound signalcorresponding to the distance from the first ultrasound transducerassembly to a predetermined segment distance from the of the firstultrasound transmitter, and analyzing a set of subsequent segments,where each subsequent segment in the set of subsequent segmentssequentially describes the received ultrasound signal from the firstultrasound transducer assembly to a distance that is one morepredetermined segment distance away from the first ultrasound transducerassembly than the previous segment.

In a still further embodiment, time-boxing the received ultrasoundsignal includes analyzing a first segment of the received ultrasoundsignal corresponding to the distance from the first ultrasoundtransmitter to a predetermined segment distance from the of the firstultrasound transmitter, and analyzing a set of subsequent segments,where each subsequent segment in the set of subsequent segmentssequentially describes the received ultrasound signal from the previoussegment to a distance that is one more predetermined segment distanceaway from the first ultrasound transmitter than the previous segment.

In yet another embodiment, the method further includes determiningwhether the stroke is an ischemic stroke or a hemorrhagic stroke basedon the received ultrasound signal.

In a yet further embodiment, determining whether the stroke is anischemic stroke or a hemorrhagic stroke includes matching the harmoniceffects to a known set of harmonic effects.

In another additional embodiment, determining whether the stroke is ahemorrhagic stroke includes identifying blood pooling by locatingharmonic effects representing microbubbles pooling in a region of thebrain for an extended period.

In a further additional embodiment, determining whether the stroke is anischemic stroke includes identifying areas where no harmonic effectsrepresenting microbubbles are present.

In another embodiment again, the microbubbles generate differentharmonic frequencies depending on the pressure that the microbubbles aresubject to, and wherein determining whether the stroke is a hemorrhagicstroke or an ischemic stroke includes measuring the frequenciesassociated with the microbubble harmonic effects, calculating anintracranial pressure of the patient based on the measured frequencies,and determining a type of stroke based on the intracranial pressure.

In a further embodiment again, the received first ultrasound signal isfurther affected by unwanted harmonic noise, and reducing unwantedharmonic noise includes transmitting a second ultrasound signal usingthe first ultrasound transmitter assembly, where the second ultrasoundsignal is 180 degrees out of phase with the first transmitted ultrasoundsignal, and filtering the first ultrasound signal to remove unwantedharmonic noise, where the unwanted harmonic noise is correlated tophase.

In still yet another embodiment, the received first ultrasound signalincludes a first peak and a second peak, where the received firstultrasound signal's first peak and second peak correspond to harmoniceffects, and wherein detecting if a stroke has occurred includeslocating the first received ultrasound signal's first peak by finding afirst inflection point in the received first ultrasound signal, locatingthe first received ultrasound signal's second peak by finding a secondinflection point in the received first ultrasound signal, and matchingthe pattern of the peaks in the first received ultrasound signal topredetermined patterns of peaks representing brains suffering fromstroke.

In a still yet further embodiment, the method further includestransmitting a second ultrasound signal using a second ultrasoundtransmitter, receiving the second ultrasound signal using at least oneof the first ultrasound receiver and a second ultrasound receiver, wherethe second received ultrasound signal includes a first peak and a secondpeak, where the second ultrasound signal's first peak and second peakcorrespond to harmonic effects, locating the second received ultrasoundsignal's first peak by finding a first inflection point in the receivedfirst ultrasound signal, locating the second received ultrasoundsignal's second peak by finding a second inflection point in thereceived first ultrasound signal, calculating the differences betweenthe first received ultrasound signal's peaks with the second receivedultrasound signal's peaks, and detecting whether a stroke has occurredbased on the calculated differences.

In still another additional embodiment, the method further includescalculating an appropriate attenuation sufficient for detecting strokes,and displaying an indicator representing if the attenuation issufficient for diagnostic testing based on the difference between acurrent attenuation and the calculated attenuation.

In a still further additional embodiment, a system for detecting strokesincludes a processor, an ultrasound transmitter element in communicationwith the processor, an ultrasound receiver element in communication withthe processor, and a memory in communication with the processor, thememory including a stroke diagnostics application, where the strokediagnostics application directs the processor to transmit an ultrasoundsignal across a patient's brain using the ultrasound transmitterelement, where the blood in the patient's brain contains microbubbles,receive the ultrasound signal using the ultrasound receiver element,calculate the differences in the received ultrasound signal from thetransmitted ultrasound signal based on microbubble harmonic resonance,and determine whether or not a stroke has occurred based on themicrobubble harmonic resonance.

In still another embodiment again, a method for placing ultrasoundtransducer assemblies on a patient for stroke detection using a portableultrasound device includes placing a first ultrasound transducerassembly at a first location on a patient's head, placing a secondultrasound transducer assembly at a second location on a patient's head,transmitting an ultrasound signal from the first ultrasound transducerassembly across the patient's head, receiving the ultrasound signalusing the second ultrasound transducer assembly, calculating theexpected amplitude of the ultrasound signal if the first and secondultrasound transducers were properly aligned, calculating the differencebetween the calculated expected and a measured amplitude of the receivedultrasound signal, and providing an indicator representing if thealignment of the is sufficient for diagnostic testing based on thecalculated difference.

In a still further embodiment again, the method further includescalculating an appropriate attenuation sufficient for detecting strokesusing a portable ultrasound device on the patient, and displaying anindicator representing if the attenuation is sufficient for diagnostictesting based on the difference between a current attenuation and thecalculated attenuation.

In yet another additional embodiment, the indicator is visually providedusing a display.

In a yet further additional embodiment, the indicator is audiblyprovided using a speaker.

Additional embodiments and features are set forth in part in thedescription that follows, and in part will become apparent to thoseskilled in the art upon examination of the specification or may belearned by the practice of the invention. A further understanding of thenature and advantages of the present invention may be realized byreference to the remaining portions of the specification and thedrawings, which forms a part of this disclosure.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a conceptual illustration of a portable ultrasound device incommunication with a variety of medical systems in accordance with anembodiment of the invention.

FIG. 2 is a rendering of a portable ultrasound device in accordance withan embodiment of the invention.

FIGS. 3A-D are renderings of a sequence of operations performed whenpreparing a portable ultrasound device for use on a patient inaccordance with an embodiment of the invention.

FIGS. 4A-B are rendering of a portable ultrasound device being used on apatient in accordance with an embodiment of the invention.

FIG. 5 is a block diagram illustrating the system architecture of aportable ultrasound device in accordance with an embodiment of theinvention.

FIG. 6A is a block diagram illustrating a first system architecture of aportable ultrasound device in accordance with an embodiment of theinvention.

FIG. 6B is a block diagram illustrating a second system architecture ofa portable ultrasound device in accordance with an embodiment of theinvention.

FIG. 6C is a block diagram illustrating a third system architecture of aportable ultrasound device in accordance with an embodiment of theinvention.

FIG. 7 is a flow chart illustrating a process for using a portableultrasound device in accordance with an embodiment of the invention.

FIG. 8 is a flow chart illustrating a process for performing self-checktests using a portable ultrasound device in accordance with anembodiment of the invention.

FIG. 9 is a flow chart illustrating a process for performing diagnostictests using a portable ultrasound device in accordance with anembodiment of the invention.

FIG. 10 is a flow chart illustrating a process for calculating varioustest parameters using a portable ultrasound device in accordance with anembodiment of the invention.

FIG. 11 is a flow chart illustrating a process for generating andproviding diagnostic support data using a portable ultrasound device inaccordance with an embodiment of the invention.

FIG. 12 is a diagram conceptually illustrating a contralateral receivingapproach to generating diagnostic support data in accordance with anembodiment of the invention.

FIG. 13 is a flow chart illustrating a process for performing acontralateral receiving approach to generating diagnostic support datain accordance with an embodiment of the invention.

FIG. 14 is a diagram conceptually illustrating an ipsilateral receivingapproach to generating diagnostic support data in accordance with anembodiment of the invention.

FIG. 15 is a flow chart illustrating a process for performing anipsilateral receiving approach to generating diagnostic support data inaccordance with an embodiment of the invention.

FIG. 16A is a chart illustrating acoustic response signals from ahealthy hemisphere in accordance with an embodiment of the invention.

FIG. 16B is a chart illustrating acoustic response signals from anafflicted hemisphere in accordance with an embodiment of the invention.

FIG. 16C is a chart illustrating acoustic response signals from anafflicted hemisphere and a healthy hemisphere compared to each other inaccordance with an embodiment of the invention.

FIG. 17A is a chart illustrating acoustic response signals in accordancewith an embodiment of the invention.

FIG. 17B is a chart illustrating exemplary acoustic response signalsfrom an afflicted hemisphere and a healthy hemisphere using acontralateral receiving approach in accordance with an embodiment of theinvention.

FIG. 17C is a chart illustrating exemplary acoustic response signalsfrom an afflicted hemisphere and a healthy hemisphere using acontralateral receiving approach in accordance with an embodiment of theinvention.

FIG. 18A is a chart illustrating acoustic response signals in accordancewith an embodiment of the invention.

FIG. 18B is a chart illustrating exemplary acoustic response signalsfrom an afflicted hemisphere using an ipsilateral receiving approach inaccordance with an embodiment of the invention.

FIG. 18C is a chart illustrating exemplary acoustic response signalsfrom a healthy hemisphere using an ipsilateral receiving approach inaccordance with an embodiment of the invention.

FIG. 19A is a chart illustrating acoustic response signals in accordancewith an embodiment of the invention.

FIG. 19B is a chart illustrating exemplary acoustic response signalsfrom an afflicted hemisphere using a combined ipsilateral/contralateralreceiving approach in accordance with an embodiment of the invention.

FIG. 19C is a chart illustrating exemplary acoustic response signalsfrom a healthy hemisphere using a combined ipsilateral/contralateralreceiving approach in accordance with an embodiment of the invention.

FIG. 20 is a flow chart illustrating a process for differentiating ableed from a blockage in accordance with an embodiment of the invention.

FIG. 21 is a conceptual diagram illustrating a portable diagnosticdevice in accordance with an embodiment of the invention.

DETAILED DESCRIPTION

Turning now to the drawings, portable ultrasound devices, and methods ofusing portable ultrasound devices are illustrated. Strokes are a leadingcause of death and serious long-term disability in the United States.When a patient in the field suffers a stroke, emergency medicaltechnicians (EMTs) are often dispatched in an ambulance to bring theperson to a hospital for treatment. For brain related injuries such as astroke, the longer a patient goes without treatment, the higher the riskof long term brain damage or death. Rapid diagnosis of stroke canquicken the application of treatment, potentially saving the patientpain and suffering.

While in the field, it is difficult for EMTs to quickly and/oraccurately diagnose a stroke. It is particularly difficult to determinethe type of stroke and where in the brain the damage has occurred.Portable ultrasound devices can be small enough to be transported in anambulance and/or be carried by hand. In numerous embodiments, portableultrasound devices are used to diagnose strokes and other braininjuries. Portable ultrasound devices can be used in the field toquickly suggest diagnoses without requiring large laboratory equipmentsuch as MRI machines or CT Scanners. Portable ultrasound devices caninstead use self-contained diagnostic equipment to suggest diagnoses.Self-contained diagnostic equipment can include, but is not limited to,transducer assemblies, positioning bands, calibration tools, and/or anyother piece of diagnostic equipment appropriate to the requirements ofgiven applications.

In numerous embodiments, portable ultrasound devices are used todetermine whether or not a patient is having a stroke or has just had astroke. Portable ultrasound devices can be utilized in conjunction withpositioning bands which are used to attach transducer assemblies to thepatient's head. In many embodiments, positioning bands are in the formof a headband with sockets for transducer assemblies and ultrasound gelpads. In numerous embodiments, two transducer assemblies are attached tothe patient's head. In a variety of embodiments, the two transducerassemblies are placed on either side of the patient's head above theears. In many embodiments, two transducer assemblies are positioned onthe temporal bones of the patient's head. However, the transducerassemblies can be placed in any orientation in accordance with therequirements of a given application. Positioning bands can be designedto apply sufficient pressure between the transducer assemblies and thehead of the patient in order to reduce the amount of time it takes forthe shape of the ultrasound gel pads and the surrounding environment(e.g. hair, skin, etc.) to settle. Ultrasound can be transmitted andreceived by the transducer assemblies.

Microbubbles can be administered to the patient as an ultrasoundacoustic markers. When microbubbles are in an acoustic field, they canbe excited and reflect ultrasound in a characteristic and recognizableway. In this way, the pattern of received ultrasound at a transducerassembly can be used to generate diagnostic support data describing, inpart or in whole, a suggested diagnosis of what type of brain injury thepatient is suffering from. For example, in numerous embodiments,diagnostic support data describes a likelihood of whether or not astroke has occurred and/or the type of stroke that may have occurred. Inmany embodiments, diagnostic support data describes any number ofmetrics and/or characteristics obtained by the portable ultrasounddevice.

In several embodiments, portable ultrasound devices can have tissueprotective applications. Tissue protective applications of the portableultrasound device can be achieved in non-emergent situations wherecerebral blood flow improvement may have benefits, such as, but notlimited to, geriatric cognitive acuity, improved hearing via improvedcochlear blood flow, or any other tissue protective applications ofultrasound and/or microbubbles as appropriate to the requirements ofgiven applications. Various ultrasound devices and techniques for usingultrasound for diagnostic and therapeutic purposes in accordance withembodiments of the invention are discussed below.

Network Connected Portable Ultrasound Devices

In many embodiments, portable ultrasound devices can be connected to avariety of other computing devices via various networks. This allows theportable ultrasound device to transmit data to other systems, such as,but not limited to, server systems and/or computers including (but notlimited to) mobile phones, personal computers, and tablet computingdevices. Information collected by a portable ultrasound device can beused to prepare additional diagnoses and treatment options for when thepatient arrives at a medical facility.

Turning now to FIG. 1 , a portable ultrasound device is showncommunicating with various other computing devices in accordance with anembodiment of the invention. The system 100 can be made of one or moreportable ultrasound devices 110 that communicate with one or morecomputers 120 and/or server systems 130 via one or more networks 140. Inmany embodiments, ultrasound medical device 110 is connected to network140 via a wireless signal. In numerous embodiments, a cellular phone canbe used as an intermediary between the ultrasound medical device 110 andnetwork 140. In a variety of embodiments, ultrasound medical device 110has a network interface which allows for connections to the network 140.The network interface can permit communications over a wired connection,and/or a wireless connection. In some embodiments, the network interfaceuses the Bluetooth wireless connectivity standard. However, any type ofwired or wireless communication method can be used as appropriate to therequirements of given applications.

Diagnostic information can include, but is not limited to, datacollected by the ultrasound medical device 110, data input by the userof the portable ultrasound device 110, or any other type of informationas appropriate to the requirements of given applications. In manyembodiments, data input by the user of the portable ultrasound deviceincludes audio recordings captured by a microphone connected to theportable ultrasound device. In some embodiments, data input by the usercan be text data. In numerous embodiments, data input by the user can beaudio and/or image data. Data transmitted by the portable ultrasounddevice can be identified by a serial number associated with the portableultrasound device and/or a time stamp corresponding to the time of use.

In certain embodiments, data is transmitted in a real time stream to anadjacent and/or remote computing device. In several embodiments, aportable ultrasound device communicates collected data in a batch uploadprocess. Server system 130 can process diagnostic information andprovide information to computer 120 and/or can transmit information backto ultrasound device 110. In some embodiments, the portable ultrasounddevice 110 transmits unprocessed collected ultrasound data to serversystem 130, where the server system 130 processes the collectedultrasound data and provides diagnostic support data. In numerousembodiments, the ultrasound medical device 110 is capable of providingdiagnostic support data without connectivity to another computingdevice.

In many embodiments, a trusted certificate system can be used to ensurethe veracity of transmitted data. In a number of embodiments,public/private key systems can be used to encrypt the transmitted data.In several embodiments, users must provide key data to the portableultrasound device in order to use the device. In numerous embodiments,portable ultrasound devices transmit data to a server system that storesdata. Server systems can analyze obtained ultrasound device data. Insome embodiments, server systems are configured to analyze data performat least one of: improving the analytic sensitivity of the system,correlating patient outcomes with diagnostic support data, predictingmedical events, correlating diagnostic support data with medicalhistory, risk profiles, and/or vital signs, correlating diagnosticsupport data with imaging methods, performing epidemiological analysis,performing cost analytics, and/or any other analysis as appropriate tothe requirements of a given application. Although a specificarchitecture for a system for communication between a portableultrasound device and various other devices is shown in FIG. 1 , anynumber of system architectures could be used in accordance with therequirements of given applications.

Portable Ultrasound Devices

Ultrasound devices in accordance with several embodiments of theinvention can be made in a portable form. Housings for portableultrasound devices can have different form factors. Portable ultrasounddevices can be small enough and light enough that they can be stored inan ambulance or other medical vehicle. In numerous embodiments, portableultrasound devices have compartments which store self-containeddiagnostic equipment. Portable ultrasound devices in accordance with anumber of embodiments of the invention can be light enough to be carriedby an EMT.

Turning now to FIG. 2 , a portable ultrasound device in accordance withan embodiment of the invention is illustrated. Portable ultrasounddevice 200 can have a housing containing circuitry used to performultrasound based diagnoses. The outside of the housing can have numerousmodifications. The portable ultrasound device 200 can have a powerbutton 210. In several embodiments, the power button 210 is a toggle, aswitch, or any other input device as appropriate to the requirements ofgiven applications. The portable ultrasound device 200 can also have oneor more input/output ports 220. Input/output ports can be universalserial bus (USB) ports, firewire ports, Ethernet ports, SD card ports,wireless connectors such as Bluetooth or WLAN antennas, and/or any otherinput/output port as appropriate to the requirements of givenapplications. In many embodiments, the portable ultrasound device 200has a control panel 230. In some embodiments, the control panel 230 canbe removed to allow access to internal components. A separate panel canalso be included in a portable ultrasound device to allow access tointernal components. The control panel 230 can have numerous buttons,switches, toggles, and/or a touch-screen interface to allow a user tooperate the portable ultrasound device 200. In several embodiments,control panel 230 allows the user to choose the type of test to beperformed, to input test parameters, to download/upload data, and tobegin/end tests. However, control panel 230 can allow any type of userinput as appropriate to the requirements of given applications.

Portable ultrasound device 200 can have a handle 240 to assist in movingthe portable ultrasound device 200. In many embodiments, handle 240 isretractable and can be made to lie flush with the portable ultrasounddevice. In this way, the handle 240 can be made in such a way that itwill not interfere with the usage or storage of the device. In a varietyof embodiments, the portable ultrasound device 200 has a compartment250. The compartment 250 can contain ultrasound diagnostic tools suchas, but not limited to, transducer assemblies, positioning bands,ultrasound gel pads, and/or any other diagnostic tool and/or medicalequipment as appropriate to the requirements of a given application.

In many embodiments, the portable ultrasound device 200 stores at leastone transducer assembly. The transducer assembly(s) can be stored incompartment 250. Transducer assemblies can also be stored in holders onthe exterior of the portable ultrasound device 200. In numerousembodiments, transducer assemblies include an ultrasound transmitterelement, and an ultrasound receiver element. In a variety ofembodiments, a coaxial dual-element ultrasound transducer can be usedthat is capable of performing the functions of both an ultrasoundtransmitter element and an ultrasound receiver element. In manyembodiments, transducer assemblies are single element transducers. Theportable ultrasound device can have a test material or pad to serve as atransmission reference media. In numerous embodiments, the test materialis stored between the transducer assemblies in such a way that the facesof the transducer assemblies are pressed against the test material. Inthis way, calibration steps can be performed with a reference media andin a standardized environment.

Portable ultrasound device 200 can have one or more display devices. Adisplay device can be lit. In numerous embodiments, multiple back lightscan be used. In some embodiments, a high power backlight and a low powerbacklight can be used. The low power backlight can be used to indicatethat user interaction is needed, and the high power display can beturned off or dimmed. A user can touch the display device to turn thehigh power backlight to a higher power so the user can more easily viewthe display. In some embodiments, the user presses a button or uses atoggle to increase the power. In a variety of embodiments, the one ormore display devices are LCD screens. In some embodiments, LED screensare used. However, any number of display devices can be used asappropriate to the requirements of a given application. In manyembodiments, portable ultrasound devices have one or more speakers toprovide audio feedback. As can readily be appreciated, the specific userinterface provided by a portable ultrasound device and/or via a portablecomputer (e.g. a mobile phone) communicating by a portable ultrasounddevice are largely dictated by the requirements of a given application.

As one can readily appreciate, the dimensions and arrangements ofspecific components of portable ultrasound device 200 as illustrated inFIG. 2 are by way of example, and the dimensions and arrangement for aportable ultrasound device is not limited by the single embodimentillustrated in FIG. 2 . The operation of various portable ultrasounddevices in accordance with a number of embodiments of the invention isdiscussed further below.

Using Portable Ultrasound Devices

In many embodiments, the portable ultrasound device utilizes positioningbands that can house transducer assemblies in a manner that allows forconsistent and reliable placement of the transducer assemblies on apatient within a tolerable range. Consistent transducer assemblyplacement on a patient's body can enable accurate diagnostics.

Turning now to FIG. 3A, a positioning band configured to be storedwithin a compartment of a portable ultrasound device is illustrated inaccordance with an embodiment of the invention. Positioning band 310 canbe stored in compartment 300. In some embodiments, more than onepositioning band can be stored in compartment 300. In numerousembodiments, compartment 300 houses transducer assemblies and/orultrasound gel pads in addition to the positioning band.

FIGS. 3B-D illustrate the preparation of a positioning band for use inaccordance with an embodiment of the invention. Positioning band 310 canbe stored in compartment 300 in a more compact, folded form. Positioningband 310 can be unfolded to create a headband shape. Positioning band310 can be manufactured in such a way that the band will telescope inorder to accommodate a variety of patient head sizes. In numerousembodiments, positioning band 310 has transducer assembly holders intowhich transducer assemblies can be socketed. In many embodiments,positioning band 310 is disposable. Positioning band 310 can besanitized and/or reused. In a variety of embodiments, a new positioningband 310 can be used for each patient. Transducer assemblies 340 can becategorized into a right side transducer assembly and a left sidetransducer assembly. In some embodiments, portable ultrasound device hastwo transducer assemblies, where one is labeled as a right transducerassembly and the other is labeled as a left transducer assembly.Positioning band 310 can also hold ultrasound gel pads 320. In numerousembodiments, ultrasound gel pads 320 have removable covers 330. In avariety of embodiments, ultrasound gel pads similar to those describedin U.S. Provisional Patent Application No. 62/452,253 can be utilized.The relevant disclosure from U.S. Provisional Patent Application No.62/452,253 is hereby incorporated by reference herein in its entirety.Positioning band 310 can have one or more positioning guides 350 to helpcorrectly position the positioning band 310 on the patient. In multipleembodiments, positioning guides 350 are designed to interface with apatient's ear. In numerous embodiments, proper placement of transducerassemblies is at the cranial temporal window of the skull. Positioningguides 350 can increase the likelihood that proper placement is achievedby making incorrect placement uncomfortable and/or inoperable. FIG. 3Dis a rendering of a positioning band fitted with transducer assemblies.

Turning now to FIGS. 4A-B, a positioning band fitted to a patient's headin accordance with an embodiment of the invention is illustrated. Inmany embodiments, positioning band 410 is placed on patient's head 400in such a way that the transducer assemblies 420 lie above the patient'sears and the positioning guides 430 do not interfere with placement. Inthis way, the portable ultrasound device can perform tests based on aknown position of the transducer assemblies 420. In a variety ofembodiments, positioning band 410 is manufactured in such a way that theportable ultrasound device will not operate when the positioning band isreversed by having features that normally protrude into a gap formedbetween the band and a patient's head, but if reversed, will lay overthe patient's ears and hold the transducer assemblies away from thehead. In many embodiments, positioning band 410 is considered reversedwhen a designated right side of the positioning band 410 is positionedon the left side of the patient's head, and/or a designated left side ofthe positioning band 410 is positioned on the right side of thepatient's head.

While positioning bands have been illustrated in the above figures,positioning bands are not essential for the use of portable ultrasounddevices. In many embodiments, transducer assemblies can be placed on apatient without the use of positioning bands. In a variety ofembodiments, positioning bands can have different form factors from theform factors illustrated in FIGS. 3A-D, and 4A-B, such as, but notlimited to, a cap, a circlet, or any other form factor that aids in thepositioning of transducer assemblies as appropriate to the requirementsof given applications. In numerous embodiments, two or more transducerassemblies can be held by positioning bands. In numerous embodiments,two pairs of transducer assemblies can be aligned approximately with thecenterline of the head, where a first transducer assembly of each pairis on the anterior side of the face, and a second transducer assembly ofeach pair is on the posterior side of the face, each pair primarilycovering a different hemisphere. In a variety of embodiments, ultrasoundtransducers can be placed on the forehead and the temples of a head.While positioning bands have been illustrated in the above figures asholding two transducer assemblies in specific locations, any number oftransducers and any number of locations can be used, including, but notlimited to, at least one transducer assembly on the forehead, the backof the head, and/or any other arrangement and number of transducerassemblies as appropriate to the requirements of a given application.

Ultrasound Device Circuitry

Ultrasound device circuitry in accordance with many embodiments of theinvention can allow a portable ultrasound device to transmit and receiveultrasound and to translate the received ultrasound signals into medicaldata. In many embodiments, the ultrasound device circuitry can helpdetermine whether the transducer assemblies are placed correctly. Innumerous embodiments, the ultrasound device circuitry can localize thestroke to a specific area of the brain and/or identify the class ofstroke that the patient has suffered.

Turning now to FIG. 21 , a conceptual diagram for a portable ultrasounddevice is illustrated in accordance with an embodiment of the invention.Portable ultrasound device 2100 includes a processor 2110. Processorscan be any logic unit capable of processing data such as, but notlimited to, central processing units, graphical processing units,microprocessors, parallel processing engines, or any other type ofprocessor as appropriate to the requirements of specific applications ofembodiments of the invention. Portable ultrasound device 2100 furtherincludes an input/output interface. In numerous embodiments,input/output interfaces are capable of interfacing with other portableultrasound device circuitry including, but not limited to, displays,ultrasound transducer assemblies, or any other circuitry used byportable ultrasound devices as appropriate to the requirements ofspecific applications of embodiments of the invention.

Portable ultrasound device further includes a memory 2130. Memory can beimplemented using any combination of volatile and/or non-volatilememory, including, but not limited to, random access memory, read-onlymemory, hard disk drives, solid-state drives, flash memory, or any othermemory format as appropriate to the requirements of specificapplications of embodiments of the invention. Memory 2130 contains astroke diagnostics application 2132. Stroke diagnostics applications candirect the processor and any relevant portable ultrasound devicecircuitry to perform ultrasound diagnostic processes such as, but notlimited to, those described below. Memory 2130 can further includemicrobubble profiles 2134 that describe the harmonic responses ofdifferent types of microbubble compositions, and/or patient data 2134describing clinically relevant information about the patient.

While a conceptual diagram for portable ultrasound devices is discussedabove with respect to FIG. 21 , portable ultrasound devices can includedifferent configurations of analog and/or digital components to enablethe collection of ultrasound data. Turning now to FIG. 5 , a blockdiagram for the circuitry of a portable ultrasound device is illustratedin accordance with an embodiment of the invention. Circuitry 500includes a microcontroller 510 connected to a signal generator 520. Incertain embodiments, the signal generator 520 can generate a sinusoidalsignal capable of driving a transducer assembly. In a variety ofembodiments, the signal generator 520 can generate a non-sinusoidalsignal capable of driving a transducer assembly. In several embodiments,the signal generator 520 is capable of modifying the signal strength andresulting transmitted signal power. In a number of embodiments, thesignal generated by the signal generator is dynamically modified basedon commands received from the microcontroller to control the outputpower of the transducer assemblies 540. In certain embodiments, thesignal generated by signal generator 520 is conveyed to the transmitelement of at least one of a set of transducer assemblies 540 via relays530. In several embodiments, the relays 530 pass the signal to one oftwo transducer assemblies 540. Microcontroller 510 can direct the relays530 to pass the signal to the transmit element of a specified transducerassembly 540.

A second relay 550 can be configured by microcontroller 510 to pass asignal from at least one receive element of transducer assemblies 540.In numerous embodiments, the second relay 550 pass a signal from onlyone receive element at a time. The signal received by second relay 550can be passed to signal conditioning circuitry 560. Signal conditioningcircuitry can be configured in such a way that the signal can bemodified to filter out DC components of the signals. In a variety ofembodiments, signal conditioning circuitry 560 amplifies the signal. Innumerous embodiments, the signal conditioning circuitry 560 down mixesthe received signal to a frequency band that simplifies subsequentsignal processing operations. The specific range can be a range at whichan analog to digital converter can sample the band limited down sampledsignal at a rate equaling or exceeding the Nyquist rate of the downsampled signal (e.g. a rate greater than or equal to twice the highestfrequency component of the band limited signal). While the signalconditioning circuitry 560 can filter the signal, additional filteringcan occur in the digital domain.

In numerous embodiments, transducer assemblies include at least oneultrasound transducer. In many embodiments, transducer assembliesinclude a first ultrasound transducer and a second ultrasoundtransducer. The first and second ultrasound transducers can be mountedin a controlled orientation within the transducer assembly. In a varietyof embodiments, the first and second ultrasound transducer are alignedco-axially and co-planar. The first ultrasound transducer can be tunedfor receiving ultrasound at a specific transmitting frequency, and thesecond ultrasound transducer can be tuned for transmitting ultrasound atspecific transmitting frequency. In a variety of embodiments, thereceiving frequency is 1,100 kHz, and the transmitting frequency rangeis 220 kHz. However, any number of frequencies, including ranges offrequencies can be used in accordance with the requirements of a givenapplication.

In many embodiments, ultrasound transducers designated for receiving andultrasound transducers designated for transmitting are separated intodifferent transducer assemblies. Further, the ultrasound transducers canoperate bidirectionally, and are not limited to only receiving ortransmitting.

The signal conditioning circuitry 560 outputs a signal that is providedto an analog to digital converter 570, which converts the signal from ananalog signal to a digital signal. In many embodiments, once the signalis digitized, additional digital filtering can be performed by themicrocontroller 510. As one can readily appreciate, a variety ofspecific circuits can be used to perform the functions described aboveas appropriate to the requirements of a given application. While anynumber of circuit configurations can be used as appropriate to therequirements of a given application, a specific example of a portableultrasound device circuitry is discussed below.

Example Portable Ultrasound Device Circuitry

Turning now to FIG. 6A, example specific circuitry for a portableultrasound device is illustrated in accordance with an embodiment of theinvention. In the illustrated embodiment, the signal generator includesa sine-wave generator 602 and a flip-flop connected to an AND gate 604.As noted above, the combination of the flip-flop connected to an ANDgate 604 and the sine-wave generator 602 can serve to control the timingof the transmission of pulses generated by the sine-wave generator 602so that pulses commence and end at zero-crossings of the signalgenerated by the sine-wave generator 602. In many embodiments, amicrocontroller can select whether the transmission starts with a risingzero-crossing or a falling zero-crossing in order to transmit pulsesthat are 180 degrees out of phase. A CPU 600 can initiate transmissionof a pulse of ultrasound via the AND gate by causing the flip-flop topass a signal from the sine-wave generator to an operational amplifier608. In the illustrated embodiment, the operational amplifier includes again control mechanism. The CPU 600 can utilize the gain controlmechanism to control the output power of the transmitted signal. Innumerous embodiments, the signal is passed through a transformer 610 toprovide impedance matching with transducer assemblies which willtransmit the signal. The CPU 600 can direct which transmit element willtransmit the signal using a first select relay 612. Transmit elementscan be components of transducer assemblies. The first select relay 612can chose between a first transducer assembly 614 and a secondtransducer assembly 616. A second select relay 618 can be utilized bythe CPU 600 to receive a signal from one of the transducer assemblies tomonitor the transmission of the signal.

A third select relay 620 can be used to receive a signal from at leastone of the transducer assemblies. As can readily be appreciated, asingle relay, multiple relays, and/or a variety of relays can be used asappropriate to the requirements of given applications. The third selectrelay 620 can transfer the received signal to a high-pass filter 622 inorder to remove any low frequency components of the signal. In numerousembodiments, a capacitor inlined to remove DC bias. The high-passedsignal can be provided to a low-noise amplifier 624 in order to boostthe signal without introducing significant amounts of additional noise.The amplified signal can be down-converted using a mixer module 626, andprovided to a low-pass filter 628 to band limit the signal eliminatinghigh frequency noise prior to digitization. The signal can be providedas an input to an operational amplifier 630 before being provided as aninput to an analog to digital converter 632. The digital form of thesignal can be stored in a memory by the CPU 600 for additional digitalprocessing. Although specific circuits are described above with respectto FIGS. 5, 6A, 6B, and 6C for generating and processing signals in anultrasound device, any number of specific circuit configurations can beused in an ultrasound device as appropriate to the requirements of givenapplications in accordance with various embodiments of the invention. Inmany embodiments, single components can perform the tasks that can bedone by multiple components. Not all components are necessary for theusage of portable ultrasound devices. For example, additionalimplantations using specific circuits are illustrated in FIGS. 6B and6C. Portable ultrasound devices can have circuitry that enables theoutput of the transducer assemblies to be regulated.

Regulating Transducer Assembly Output

Components of portable ultrasound devices can be used to control thestart of ultrasound transmission in such a way that there is low andpredictable latency between the “start” signal and the actual beginningof the transmission signal. In numerous embodiments, receiving elementsare triggered to begin receiving ultrasound by the “start” signal. Lowand predictable latency can enable ultrasound transmission that ishighly synchronized for time/spatial precision. It can be important toknow the precise start of a transmitted signal as well as the frequencyand amplitude.

Analog systems often cannot immediately transmit a target frequency andamplitude without time to stabilize. This period is called the “ring up”period. Similarly, a “ring down” period can occur when a transmission isturned off. When the beginning and end of a transmitted signal is at thezero voltage (crossover) point in the waveform, the transientdisturbance of the circuit can be minimized, and the circuit can rapidlymove to a desired amplitude with increased frequency conformance. In avariety of embodiments, the ultrasound device circuitry allows for thestart of transmission to occur randomly at any phase angle, and thefirst cycle of the transmission has frequency content that is variabledepending on the phase angle at the start. In several embodiments,however, phase angle is controlled to create ultrasound device circuitryin which the ring up and ring down characteristics of the transmittedsignal are repeated from one transmission to the next. In certainembodiments, phase angle is controlled using a flip-flop inline betweenan oscillating source and the amplification section of the transmitcircuit. The flip-flop can act to allow the sinusoidal signal generatedby the oscillator circuit through only at a zero crossing. In this way,the signal that is amplified and transmitted to the transducer assemblycan always start at a zero crossing of the phase angle, providingpredictable ring up and ring down behavior. Ring up and ring downperiods can be experienced by microbubbles as they are exposed to andremoved from ultrasound stimulation, respectively. As is discussedfurther below, the ability to predict the ring up and ring down periodcan provide significant benefits with respect to the use of signaltiming in functions including (but not limited to) stroke localization.Portable ultrasound devices can be used for a variety of medicalpurposes, such as, but not limited to, stroke detection and localizationare described below.

Methods for Operating Portable Ultrasound Devices

Portable ultrasound devices can perform a variety of operations to allowfor accurate data generation. In many embodiments, portable ultrasounddevices automatically perform a variety of operations prior togenerating diagnostic support data.

Turning now to FIG. 7 , a process for using a portable ultrasound deviceis illustrated. The process 700 for using a portable ultrasound deviceincludes powering (710) the system. Powering (710) on a portableultrasound device can be achieved by pressing a switch, a button, or anyform of power toggle as appropriate to the requirements of givenapplications. In many embodiments, the portable ultrasound deviceperforms (720) self-check tests to verify that the device is in workingcondition and is safe to use. The portable ultrasound device can furtherperform (730) diagnostic tests and generate (740) diagnostic supportdata based on diagnostic test results. The diagnostic support data canbe provided (750) in any number of ways including (but not limited to)display via a user interface and/or audio output. In numerousembodiments, the diagnostic support data is transferred to a computerand/or server system. In many embodiments, the diagnostic support datacan be output to a storage device similar to those described in FIG. 1via the input/output port.

While a method for using portable ultrasound devices has been outlinedabove, one of ordinary skill in the art would recognize that portableultrasound devices have numerous applications which may requirereordering of steps, removal of steps, and/or addition of steps asappropriate to the requirements of given applications. The followingsections will generally discuss processes for generating suggesteddiagnoses and performing diagnostic tests based on microbubble harmonicresponses. The diagnostic processes then serve as a backdrop fordiscussing the importance of various self-check tests, calibrationsteps, and additional diagnostic processes that can be performed byportable ultrasound devices in accordance with various embodiments ofthe invention.

Using Microbubbles as Acoustic Markers

Microbubbles can be used with portable ultrasound devices as acousticmarkers. When microbubbles are exposed to ultrasound, they can resonateand generate harmonic signal responses. Microbubble harmonic responsescan be detected by portable ultrasound devices, and portable ultrasounddevices can determine the position of microbubbles based on the detectedharmonic responses. In some embodiments, microbubbles are administeredas a bolus. In many embodiments, microbubbles are administered graduallyusing an IV. In a variety of embodiments, microbubbles are administeredorally. In some embodiments, microbubbles are administered as aninhalant Microbubbles can be administered to the patient multiple timeswhile the portable ultrasound device is in use. The portable ultrasounddevice can alert the user that it is ready for microbubbles to beadministered to the patient. The alert can be visual using a display ora light, and/or auditory using a speaker. In numerous embodiments,medical grade microbubbles are used for the diagnostic process.Microbubbles can have characteristic signal responses per unit ofapplied acoustic pressure and a characteristic latency for the signalresponse. Because microbubbles are carried by the blood, the microbubbleharmonic responses can be used to measure blood movement in the brain.

In numerous embodiments, a portable ultrasound device monitors whethermicrobubbles have been introduced too early during “baseline”measurements. Early administration of microbubbles can be detected bychecking for at least one frequency and/or amplitude marker that is areliable indicator of the presence of microbubbles (e.g. a harmonic ofthe ultrasound frequency that is typically detected in the presence ofmicrobubbles). In some embodiments, the portable ultrasound devicechecks whether or not microbubbles have been introduced properly duringa test measurement by checking for characteristic microbubble harmonicresponses and/or amplitude marker that is known to be consistentlypresent when microbubbles are present. In a variety of embodiments, theformulation of the microbubbles introduced can be derived by measuringtheir characteristic microbubble responses.

Bolus injection of microbubbles is typically characterized by a rapidrise in microbubble concentration in the bloodstream and tissue forseveral seconds, and then receding from the bloodstream relativelyquickly. The entry and rise of concentration of microbubbles is called a“wash-in,” whereas the process of receding is called a “wash-out.”Wash-in typically can begin within a few seconds of injection, and canreach a peak within 5 and 10 seconds. However, depending on the rate ofblood flow, it can be a longer or shorter period of time. Wash outoccurs over a longer period than wash-in to get the majority ofmicrobubbles out of the patient's system, but can be longer or shorterdepending on the rate of blood flow and condition. While not allmicrobubbles might not be washed out after this period, the portableultrasound system can count the microbubbles as receded once themeasured concentration has been reduced past a certain threshold. Insome embodiments, the threshold is 70% of a peak harmonic amplitudeobserved during and/or following wash-in, however any threshold can beused as appropriate to the requirements of a given application. However,a wide variety of thresholds can be used as appropriate to therequirements of specific embodiments of the invention. The amount ofreduction in observed harmonics within a received signal associated withthe presence of microbubbles can be obtained by comparing the peak ofthe detected microbubble wash-in with the baseline acousticmeasurements. Further, because the wash-in, wash-out period isrelatively short, the portable ultrasound device can detect thecommencement of a wash-in event. In this way, the portable ultrasounddevice need not rely on a user input to determine when an injection ofmicrobubbles is administered.

By measuring patterns of blood flow, a diagnosis can be calculated. Washin/wash out rates for each hemisphere can be compared to each other. Inmany embodiments, comparison between hemispheres can be used instead ofdefault threshold measurements. Methods for generating diagnosticsupport data are discussed below.

Generating Diagnostic Support Data Using Portable Ultrasound Devices

Portable ultrasound devices can generate diagnostic support data basedon diagnostic test results. The processor of the portable ultrasounddevice can be configured by an ultrasound diagnostic application toacquire diagnostic test data from diagnostic tests and process saiddiagnostic test data to produce diagnostic support data. The processorcan transmit the diagnostic test data to a computer or server system tobe processed to produce diagnostic support data. Diagnostic support datacan include a calculated diagnosis. Calculated diagnoses can begenerated based on recognizable patterns associated with known injuries.Patterns can be recognized by measuring microbubble harmonic responseswithin the patient's blood. Several methods for pattern recognition arediscussed further below.

When a large bleed occurs the ambient pressure in the hemisphere oftenrapidly elevates above normal and initially there can be excessive bloodflowing into a cavity of the hemisphere without flowing properly intothe surrounding tissue. Later, the average pressure can elevate evenmore substantially and the excessive blood flow into the cavity subsidesand drops below normal due to the elevated pressure. In this scenario,the blood in the cavity tends to stay “trapped” for a long time.Microbubbles can be injected into the blood supply early in the bleed,causing a large concentration of microbubbles to flow into the cavityand be trapped there while surrounding tissue has a lower concentration.As pressure builds, the microbubble amplitudes can be reduced comparedto the expected normal amplitudes based on concentration. Asconcentration increases, the signal response is typically highest forthe region of trapped blood compared to other regions in thathemisphere.

Microbubbles can also be injected into the blood supply late in thebleed. In a late bleed, less blood is likely to flow into the cavity andthe microbubble concentration can drop to a level comparable to orslightly higher than the surrounding tissue. Therefore, the microbubblesignal responses across the hemisphere are expected to be more uniform,but at a lower concentration due to the impairment of blood supply basedon elevated pressure. The described signatures can be used to diagnose abrain hemorrhage, and can be used to diagnose the stage of the bleed. Insome embodiments, a portable ultrasound device will attempt to determineif there is a bleed before checking if there is a blockage.

In many embodiments, the diagnostic support data includes aclassification of the type of stroke detected. An ischemic stroke can besignified by a relatively normal response pattern on one side of thebrain, and a blockage pattern in the opposite hemisphere. Hemorrhagicstrokes can be signified by a lack of blockage patterns, but detectionof some high volumes of blood and some lower volumes of blood indifferent regions of the hemispheres can indicate a bleed.

In many embodiments, the portable ultrasound device can detect whenmicrobubbles are destroyed in the acoustic field. If microbubbles aredestroyed in the acoustic field, then replenishment time can indicatethat there is a hemorrhage. Since blood is not being replenished quicklyin the high-pressure volume outside the bleed, then after microbubblesin the volume are destroyed, microbubble signatures ramp up more slowlyin the area of high-pressure. Further, replenishment time can be anindicator of perfusion condition, and can be measured by varying theultrasound pulse repetition time to determine the necessary time formicrobubbles to repopulate the sonicated volume. In some embodiments,replenishment analysis can be performed without destroying microbubbles.A second bolus of microbubbles can be introduced after wash-out of thefirst bolus in order to mimic the replenishment effect described above.

While several injury patterns are described above, portable ultrasounddevices can be used to associate any number of injury patterns tospecific injuries as appropriate to the requirements of givenapplications. Many injury patterns can be detected with appropriateconfiguration of a portable ultrasound device in accordance with variousembodiments of the invention based on the patterns of blood flowresulting from the injuries. By way of example, a comparison of anidealized standard healthy brain pattern vs. an injured brain pattern isillustrated in FIGS. 16A-C in accordance with an embodiment of theinvention. FIG. 16A illustrates a harmonic response signal over timefrom a healthy hemisphere. FIG. 16B illustrates a harmonic responsesignal from an afflicted/injured hemisphere in accordance with anembodiment of the invention. FIG. 16C illustrates a comparison of theharmonic response signals of FIGS. 16A and 16B.

Turning now to FIG. 11 , a process for generating diagnostic supportdata based on diagnostic test data is illustrated in accordance with anembodiment of the invention. Process 1100 includes computing (1110)normalized left vs. right microbubble harmonic amplitudes. Normalizedmicrobubble harmonic amplitudes can be compared (1120) to predeterminedthresholds, and in some embodiments, left and right hemispheres of thebrain are discerned (1130). Precision spatial segmentation can beapplied (1140) to the threshold comparisons in order to localizeinjuries. If microbubbles were administered as a bolus, then the wash indelays and amplitudes can be compared (1150). Generating (1160)diagnostic support data including a suggested diagnosis based on theresults of the processed diagnostic tests. Portable ultrasound devicescan provide (1170) diagnostic support data generated based on thediagnostic tests. Portable ultrasound devices can provide diagnosticsupport data. In some embodiments, the suggested diagnosis is providedvia a display. However, the diagnostic support data can be provided in avariety of methods, including, but not limited to, storing data on anon-transient machine readable medium, uploading data to a computer,uploading data to a server system, uploading data to a mobile phone,and/or communicating data via any other information transfer protocol asappropriate to the requirements of a given application.

While a specific process for generating diagnostic support data isdescribed above, one of ordinary skill in the art would recognize thatthere are numerous ways to generate diagnostic support data fromdiagnostic tests and analysis in accordance with the requirements ofgiven applications. Examples of processes for generating diagnosticsupport data from different diagnostic tests are described below.

Generating Diagnostic Support Data from Contralateral ReceivingDiagnostic Tests

Different diagnostic tests can produce different types of data.Contralateral describes a configuration in which two objects are on theopposite side of the body from each other. For example, if an ultrasoundtransmitter element is placed on the right side of a patient's head, andan ultrasound receiver element is placed on the left side of thepatient's head, the transmitter and receiver would be contralaterallyoriented. In contrast, if both the transmitter and receiver elementswere on the right side of the patient's head, they would beipsilaterally oriented. Diagnostic tests can be performed usingcontralateral, ipsilateral, or any other type of configuration, such as,but not limited to, multi-point arrangements including transmitters onthe center-line of the body, as appropriate to the requirements ofspecific applications of embodiments of the invention. However,regardless of the type of diagnostic test performed, microbubbleharmonic signals will be dominated by the signal generated bymicrobubbles on the hemisphere of the brain closest to the transmittingtransducer assembly when the focal point of peak negative pressure isdesigned to be at or near the interface of the transducer assembly. Innumerous embodiments, this is caused by the high energy focal area ofthe transducer assembly overlapping large blood vessels closest to thetransducer assembly. This phenomenon is referred to as “transmit sidebias” of the microbubble signal profile. Transmit side bias can beachieved by inducing a beam shape and placing transducer assemblies onthe head to approximately align with large blood vessels. Transmit sidebias can be utilized in generating diagnostic support data. A diagnostictest contralateral receiving approach uses a transmitting transducerassembly and a separate receiving transducer assembly. Methods forperforming the contralateral receiving approach are described in a belowsection.

Turning now to FIG. 17A, actual microbubble levels in an exemplary brainwith an afflicted left hemisphere and a healthy right hemisphere areillustrated in accordance with an embodiment of the invention. Incomparison to FIG. 17A, FIG. 17B illustrates received harmonic responsesignals received when transmitting on the healthy side of the brain inaccordance with an embodiment of the invention. FIG. 17C illustratesreceived harmonic response signals when transmitting on the afflictedside of the brain in accordance with an embodiment of the invention.

In the example illustrated in FIG. 17B, due to transmit side bias, whentransmitting on the afflicted side, the signal levels from the afflictedhemisphere will be raised, and the signal levels from the healthyhemisphere will be lowered from their actual levels. Similarly, in theexample illustrated in FIG. 17C, when transmitting on the health side,the signal levels from the healthy hemisphere will be raised, and thesignal levels from the afflicted hemisphere will be lowered compared totheir actual levels. The net signal received by a transducer assembly isa combination of what is illustrated in FIGS. 17B and 17C. Of note isthe “double peak” profile which is expected to occur at minimum whentransmitting on the afflicted side. Presence of a double peak canindicate a stroke because of the delayed wash-in on one side of thebrain. However, in addition to the knowledge of the double peak, the twographs in FIGS. 17B and 17C can be compared with respect to amplitude inorder to refine and confirm results. The increase in amplitude of peakone when transmitting on the right (healthy) side indicates that it isthe healthy hemisphere, whereas the decrease in amplitude of peak twoindicates that it is the afflicted hemisphere. Further, by averaging thegraphs from transmitting on both sides, a graph similar to the actualmicrobubble signal as illustrated in FIG. 17A can be generated.

In cases where the second peak is difficult to identify, the searchspace can be refined by looking for an “elongated” peak time-shiftedfrom the first peak. The elongated peak can be further identified by amore gradual decline in the slope of the curve following the secondpeak. Further, the width of the curve is generally wider as compared tothe height of the peak when transmitting from the side of the afflictedhemisphere. A boundary can be identified between the peaks as the pointwhere the amplitude neither rises nor falls. This neutral point canrepresent the boundary between the part of the curve that is dominatedby the healthy hemisphere responses and the part of the curve that isdominated by the afflicted side responses.

In numerous embodiments, when the second peak is difficult to identify,once the first, temporally earlier peak has been identified, the rollingaverage of the continuous slope of the curve moving forward can beanalyzed for the presence of the second, temporally later peak using“shoulder detection.” In a variety of embodiments, shoulder detectioninvolves identifying potential changes in the slope after the first peakconsistent with the potential presence of a second peak. Once such alocation has been identified, the portion of the curve after thelocation that is the same length as the distance from the first peak tothe identified location can be analyzed for the presence of any otherpotential second peaks. In numerous embodiments, if there is no secondpeak within that distance, it can be assumed that the second peak hasbeen located. However, any distance to the right of the located secondpeak can be analyzed as needed. In numerous embodiments, whentransmitting on the afflicted slide, the second peak will be higher, theslope between the two identified peaks will be shallower, and the slopeto the right of the second peak will be more negative than when comparedto a transmission on the unaffiliated side.

In cases where the afflicted side has so little perfusion that thesignal is effectively undetectable, a case can occur where only“healthy” curves are observable. This does not prevent the ability todetect and localize a stroke. If the increase in signal when switchingfrom left transmitting to right transmitting is too large to beexplained by side-to-side tolerance ranges, then the portable ultrasounddevice can conclude that the signals are only being generated from oneside.

While specific methods for generating diagnostic support data using acontralateral receiving approach are discussed above with respect to aspecific example, the contralateral receiving approach can be utilizedwith any number of brain afflictions in accordance with the requirementsof a given application. Portable ultrasound devices are not restrictedto only using one approach. A method of generating diagnostic supportdata using an ipsilateral receiving approach is discussed below.

Generating Diagnostic Support Data from Ipsilateral Receiving DiagnosticTests

The ipsilateral receiving approach involves using a single transducerassembly to both transmit and receive per hemisphere. The ipsilateralreceiving approach in combination with time-boxing of received signalsenables the portable ultrasound device to analyze only certain regionsof the brain. In numerous embodiments, time-boxed signals are portionsof a signal that occur between two points in the time-domain of thesignal. In numerous embodiments, the two points correspond to the timeat which the signal describes a region of interest. However, unwantedharmonics are generally generated at the boundary of the flesh and skullas ultrasound begins to propagate. These harmonics introduce noise at apoint very close to the transmitting transducer assembly. Because thetransmitting transducer assembly is also the receiving transducerassembly in the ipsilateral receiving approach, received signals can benoisy with unwanted harmonics from the skull boundary.

Turning now to FIG. 18A, actual microbubble levels in an exemplary brainwith an afflicted left hemisphere and a healthy right hemisphere areillustrated in accordance with an embodiment of the invention. FIG. 18Billustrates the signal received from only the left hemisphere whentransmitting on the left side using time-boxing in accordance with anembodiment of the invention. The ipsilateral signal is distorted byunwanted harmonic noise. Similarly, FIG. 18C illustrates the signalreceived from only the right hemisphere when transmitting on the rightside using time-boxing in accordance with an embodiment of theinvention. Again, the ipsilateral signal is distorted by unwantedharmonics.

Unwanted harmonics can be mitigated to an extent by using techniquesdescribed below. In addition, a combined ipsilateral/contralateralreceiving approach can be utilized in order to mitigate weaknesses ofboth approaches.

Combined Ipsilateral/Contralateral Receiving Approach

Turning now to FIG. 19A, actual microbubble levels in an exemplary brainwith an afflicted left hemisphere and a healthy right hemisphere areillustrated in accordance with an embodiment of the invention. In orderto obtain an estimate of the actual blood flow, both the ipsilateral andcontralateral receiving approaches can be used in tandem. In manyembodiments, sets of interleaved measurements are obtained bytransmitting and receiving signals both ipsilaterally andcontralaterally. In numerous embodiments, the periodicity of themeasurements are sufficiently fast so that the plots over time can begenerated for transmissions on both the right and left transducerassemblies with both ipsilateral and contralateral measurements.Portable ultrasound devices can generate these plots with resolution noworse than one measurement per second for each plot. The contralateralmeasurements can be analyzed for the presence of double peaks. As notedabove, the presence of double peaks indicates a stroke conditionsomewhere in the brain. Using techniques similar to those describedabove with respect to the contralateral approach, an afflictedhemisphere can be identified.

From the contralateral data, the time-box for each peak can beidentified. These time-boxes can be overlaid onto ipsilateral dataplots. FIG. 19B illustrates an exemplary ipsilateral plot for anafflicted hemisphere with overlaid time-boxes generated fromcontralateral data in accordance with an embodiment of the invention,and FIG. 19C illustrates an exemplary ipsilateral plot for a healthyhemisphere overlaid with time-boxes generate from contralateral data inaccordance with an embodiment of the invention. In numerous embodiments,it is difficult to locate peaks using ipsilateral data alone due tounwanted harmonics. By comparing the amplitudes of the signal within thetime-boxes for each of the right side and left side ipsilateral plots,further confirmation of which hemisphere is afflicted can be generated.In many embodiments, for each ipsilateral plot, the time-box containinga peak will show an average amplitude higher than the average amplitudeof the time-box not containing a peak despite any distortion orinaccuracy created by unwanted harmonics because the unwanted harmonicstend to be relatively stable for short periods of time such as the timebetween time-boxes of the peaks.

In certain situations, ipsilateral data on one side can have a very lowamplitude resulting in a signal that is indistinguishable from the noiseof the unwanted harmonics. This can be caused by a severe strokecondition. Under severe stroke conditions, the contralateral plots maynot show a double peak because the signal levels on the afflicted sideare too low. As a result, contralateral plots can appear to reflect ahealthy brain. However, the ipsilateral plot would show a strokecondition based on amplitude comparisons, but the analysis may not havesufficient confidence. In order to resolve the disparity, several stepscan be taken. In many embodiments, based on the amplitude of thecontralateral data and the healthy side ipsilateral data plus themaximum expected tolerances between the two sides, the minimum signallevel of the side with a low signal is calculated as if the side withthe low signal level were healthy. The minimum expected signal level canbe compared to the levels of noise to determine if the minimum signallevel can be completely masked under the noise floor. In numerousembodiments, if the minimum signal level is still expected to appearabove the noise floor, but it does not, then a likely stroke on thatside is determined. In a variety of embodiments, if the minimum healthysignal level is expected to be masked by the noise floor, then theoutcome is ambiguous, and a repeat test can be recommended.

While certain processes for generating diagnostic support data have beendiscussed above, any number of different methods, including, but notlimited to, performing the above processes with different ordering canbe used in accordance with the requirements of a given application. Asnoted above, not only can diagnostic support data indicate whichhemisphere is afflicted, but portable ultrasound devices can determinethe type of stroke a patient is afflicted by. Methods for determiningthe type of stroke a patient is afflicted by are described below.

Differentiating Hemorrhagic Versus Ischemic Strokes

There are two main different types of strokes. Hemorrhagic strokes occurwhen there is a bleed occurring in the brain, often due to a bursting ofa vein or artery. Ischemic strokes occur when there is a blockage in anartery or vein resulting in a region of the brain suffering frominadequate blood supply. In numerous embodiments, portable ultrasounddevices can determine when there is a bleed vs a blockage using manydifferent methods.

In many embodiments, discrimination between a bleed and a blockage canbe achieved using time-pattern analysis. In general, bleeds can presentas a brief drop in vascular pressure and flow of blood into cranialspace as blood flows out of the arterial vessel and pools in theinterstitial space. As excess blood flows, intracranial pressure rises.The rise in pressure impedes the blood flow into the cranial space afterpressure is above normal levels. This pressure level is generallyachieved within minutes of onset, but can vary with bleed amount. Thevolume of blood in the cranial space and the corresponding rise inpressure continues for a long period of time. In many cases, this can behours. Based on this sequence of events, it is expected that the bloodsupply into the cranial space in the afflicted hemisphere will brieflybe higher than normal, then will pass through a normal range, and thenbecome lower than normal.

Throughout the process, the perfusion to the tissue is reduced and bloodflow out of the hemisphere is correspondingly reduced. Because the bleedcreates a pooled blood volume in the cranial space, blood containingmicrobubbles post bolus injection mixes with pooled blood from thehemorrhage event prior to flowing out. As a result the pooled blood willaccumulate a partial concentration of microbubbles for a significantperiod of time. As such, the wash-out pattern of a hemorrhage will besignificantly longer than a healthy brain.

Turning now to FIG. 20 , a process for performing a time-patternanalysis for determining a bleed vs. a blockage is illustrated inaccordance with an embodiment of the invention. Process 2000 includes,for the wash-in/wash-out pattern of each hemisphere, calculating (2010)the peak point, calculating (2020) the rise point, and calculating(2030) the recession point for each hemisphere. The peak point is thepoint on the wash-in/wash-out curve (harmonic response measurements) atwhich the harmonic response peaks. The rise point can be defined as anarbitrary point along the rising edge of the wash-in/wash-out curvebefore the peak point. In many embodiments, the rise point can bearbitrarily set at 50% of the peak. However, any arbitrary rise pointcan be chosen in accordance with the requirements of a givenapplication. The recession point can be defined as an arbitrary pointalong the falling edge of the wash-in/wash-out curve after the peakpoint. In numerous embodiments, the recession point can be arbitrarilyset at 50% of the peak. However, any arbitrary recession point can bechosen in accordance with the requirements of a given application.

Process 2000 further includes calculating (2040) rise time as thedifference from the rise point to the peak point, and calculating (2050)recession time as the difference from the peak point to the recessionpoint. In many embodiments, the value of the rise time plus the value ofthe recession time is called the half peak full width parameter. Innumerous embodiments, higher pressures are indicated by a smaller halfpeak full width parameter. A ratio between the rise time and therecession time can be calculated (2060). The rise/recession ratio can beused to characterize (2070) the brain condition. In many embodiments,the recession time will be longer during a bleed, meaning therise/recession ratio will be lower than for a blockage or a healthycondition. In the event of a blockage, the rise time can be elongated.In numerous embodiments, a predetermined threshold ratios can be used todetermine which type of stroke has occurred. In numerous embodiments,the predetermined threshold can be changed via an input to the portableultrasound device.

In addition to time-pattern analysis, cranial pressure can be used todetermine whether a bleed or a blockage has occurred. Microbubbles canhave acoustic responses that are dependent upon pressure. In manyembodiments, pressure influenced acoustic responses change depending onthe type of microbubble. In many embodiments, subharmonics and/orsuperharmonics are influenced by pressure. However, in numerousembodiments, normal harmonic frequencies are influenced by pressure. Bymeasuring changes in harmonic response known to be caused by pressurechanges, bleeds and blockages can be differentiated. As noted above,bleeds result in changes in intracranial pressure, whereas blockages canhave their own distinct patterns of pressure when compared to healthyhemispheres.

In many embodiments, the changes in harmonics can be used to determinecerebral perfusion pressure (difference between the mean arterialpressure and the intracranial pressure). In numerous embodiments, thecerebral perfusion pressure is inversely correlated with mean transittime (i.e. the time it takes for the microbubbles to wash-in/wash-out).In a variety of embodiments, low cerebral perfusion pressure indicates ableed. Mean transit time can also be correlated to the half peak fullwidth parameter described above. Higher pressures can cause smaller halfpeak full width values. By way of example, if an arbitrary healthy brainis assigned a half peak full width parameter of 100 units, if onehemisphere has a value of 100 and the other has a value of 40, theaffected side has elevated pressure indicating a bleed. If onehemisphere has a value of 100 and the other has a value of 140, theaffected side has reduced pressure indicating a blockage. In numerousembodiments, general blood pressure measurements from a blood pressurecuff can be incorporated into calculations

Further, spatial patterns can be used to differentiate between bleedsand blockages. Harmonic responses across spatial slices of eachhemisphere can be determined, and the resulting slices from each sidecan be compared. Methods for performing spatial segmentation can befound below. If there is a known pattern for a healthy brain for eachslice is known, then a blockages and bleeds can be differentiated. Whena blockage occurs, there can be a reduction in signal for each slice ina hemisphere consistent across each slice in that hemisphere becauseblockages tend to impact blood flow across an entire hemisphere. In theevent of a bleed, a certain region can have significantly morevariability as blood pools in different locations in the hemisphere. Thedifference between consistency and variability as contrasted to ahealthy pattern can be used to distinguish a bleed versus a blockage.

While numerous methods of differentiated bleeds and blockage, any numberof methods, including a combination of any of the above methods can beused in accordance with the requirements of a given application.Further, as noted above, higher quality diagnostic support data can begenerated in the absence of unwanted harmonics. Methods for reducingunwanted harmonics are discussed below.

Reducing Unwanted Harmonics

There are numerous ways portable ultrasound devices can be used thatreduce the amount of unwanted harmonics. In many embodiments, pulseinversion is utilized to measure and detect unwanted harmonic signals inorder to filter them out. Under a pulse inversion scheme, a first pulseof ultrasound can be transmitted, and then shortly after, a second pulsecan be transmitted such that the second pulse is 180 degrees out ofphase with the first pulse. As a result, unwanted harmonics from thefirst pulse will be 180 degrees out of phase with the unwanted harmonicsfrom the second pulse. Microbubble harmonics will not be cancelled outbecause microbubble harmonics do not have high correlation between theirphase angle and the transmission phase. In some embodiments, microbubblecomposition is chosen based on their harmonic properties to furtherreduce the correlation. Using this technique, unwanted harmonics can beidentified and filtered out of the return signals. In many embodiments,odd harmonics are fully cancelled out, where even harmonics are doubledin amplitude when the signals are added together. However, by comparingthe signals before and after the application of pulse inversion, thedoubled even harmonics can be filtered out. In numerous embodiments, thefundamental signal being transmitted by the transducer assembly is at220 kHz. In this situation, odd harmonics such as 1,100 kHz (the fifthharmonic) is cancelled out, whereas the 880 kHz (the fourth harmonic)and 1,320 kHz (the sixth harmonic) harmonics are doubled. In a varietyof embodiments, specific circuitry that enables transmission ofultrasound at a specific phase can be incorporated into to portableultrasound devices to enable pulse inversion. In many embodiments, thephase angle can be modified in order to reduce unwanted harmonics and toincrease the amount of energy that penetrates the skull.

A system that approximates pulse inversion using signal processing canalso be utilized. In many embodiments, the portable ultrasound device isconfigured to determine the amplitudes of the unwanted harmonicsindependent of the microbubble harmonics after every individual pulse.In many embodiments, each pulse is approximately 50 microseconds, andthe data being received is a time series lasting approximately 160microseconds. In numerous embodiments, the data being received is a timeseries lasting a time approximately equal to the addition of the pulsetransmit time, the time for the signal to cross the entire brain, andthe ring up period of the microbubbles. However, any length of pulse andtime series can be used as appropriate to the requirements of a givenapplication. Amplitudes can be determined by measuring the reflectedfundamental frequency which is correlated to the amplitudes of thereceived unwanted harmonics. Phase angles of the unwanted harmonics canbe measured by analyzing time-boxed slices of data at the beginning ofthe time series prior to the microbubble harmonics being received. Undera 50/150 microsecond scheme, this period is approximately the first 20microseconds. If data collected during this period is inaccurate, thephase angle relationship can be determined by using the phase angle ofthe reflected fundamental frequency as a proxy. Phase angle can furtherbe determined by transmitting at random phase angles and averaging theresponses to achieve consistency in unwanted harmonics. Using theamplitudes and phase angles of the unwanted harmonics, the unwantedharmonics can be filtered out of the total received signal to reflectonly the microbubble harmonics of interest.

In many embodiments, transducer assembly positioning can be used toreduce unwanted harmonics. Transducer assemblies can be arranged in sucha way that the transmit and receive transducers are separated in aconfiguration where the spatial orientation of the transmit field andreceive field are known. In numerous embodiments, transmitted ultrasoundis mostly contained in a directional field. A receiving transducerassembly can be positioned in such a way that it is not directly in, ornot in, the transmitting transducer assembly's ultrasound field.Harmonic responses generated by microbubbles are generally emitted inrandom directions. As such, the receiving transducer assembly will stillreceive the desired harmonic responses, while reducing unwantedharmonics that are directional, such as harmonics reflected from theskull boundary. In many embodiments, receiving transducer assemblies canbe arranged in such a way that they detect harmonics primarily from onehemisphere, while remaining outside or on the periphery of thetransmitted ultrasound field.

Portable ultrasound devices can use time-boxing to reduce unwantedharmonics. In many embodiments, specific segments of received ultrasoundsignals have reduced unwanted harmonics due to the different parts ofthe head that the ultrasound is traversing. For example, for the first40 microseconds after transmission of ultrasound by a transmittingtransducer assembly, no ultrasound may have reached the receivingtransducer assembly. Approximately the next 10 microseconds can containunwanted harmonics originating from the skull boundary. The next 40microseconds can contain mixed signals from microbubble harmonics andunwanted harmonics from various sources. The following 60 microsecondscan contain predominantly microbubble harmonic signals. While specifictimes have been discussed in the above example, any number ofmicroseconds or range of microseconds may constitute an appropriateestimate of different signal responses depending on the patient,environmental factors, and equipment used. In many embodiments, portableultrasound devices can estimate appropriate time-boxing points based ontest signals.

Time-boxing can be used to clean up signals and/or speed up analysis byprocessing only valuable signal data. In numerous embodiments, the skullboundary harmonic responses extracted from the appropriate time-box canbe used to demix the signal of the next time-box containing mixedsignals. In this way, the signal in the mixed time-box can be cleaned.Further, by time-boxing received signals, unwanted harmonics generatedfrom the interface between the transducer assembly and the patient (forexample air bubbles trapped in the gel) can be ignored or otherwiseutilized to indicate that there are problems at the interface.

While pulse inversion and signal processing techniques are discussedabove with specific reference to an ipsilateral approach, pulseinversion can be used in any number of receiving approaches, including,but not limited to contralateral receiving approaches, or combinedipsilateral/contralateral receiving approaches. Accuracy of microbubbleharmonic response analysis can be greatly increased by determining anormalized microbubble harmonic amplitude. Methods for normalizingmicrobubble harmonic amplitudes are described below.

Normalizing Microbubble Harmonic Amplitudes

A baseline harmonic amplitude can be calculated by a portable ultrasounddevice. Because each patient can have a different cranial thickness,different brain morphology, different brain density, or a number ofother biometric idiosyncrasies, harmonic amplitudes may be differentacross different patients. In many embodiments, calculating baselineharmonic amplitudes allows the portable ultrasound device to detectabnormal brain morphologies. In numerous embodiments, the portableultrasound device can compensate for abnormal brain morphologies.

Normalized microbubble harmonic amplitudes can be compared topredetermined thresholds, including, but not limited to, baselinethresholds. Establishing predetermined thresholds can be difficult, andthere are multiple ways to determine the thresholds. One method caninclude performing measurement tests on cadavers to determine howclosely values measured differ between the two hemispheres of the brainwhen both sides are perfused with solutions of similar microbubbleconcentrations. By performing this test on a statistically significantsample size, statistical calculations can determine the amount of marginnecessary in order to be highly confident that nearly all heads wouldfall into the resulting range. However, there are many ways that thesethreshold values can be determined in accordance with the requirementsof given applications.

In many embodiments, the portable ultrasound device maintains datadescribing at least one baseline harmonic response. By comparingacquired diagnostic support data describing the location of microbubbleresponses across the brain of the patient to the baseline harmonicresponses acquired in the absence of microbubbles, normalizedmicrobubble harmonic amplitudes can be identified.

The portable ultrasound device can store one or more profiles ofmicrobubble characteristics which correspond to microbubblesadministered to the patient. Profiles of microbubble characteristics caninclude, but are not limited to, signal responses per unit of appliedpressure, latency for the signal response, predetermined thresholds, orany other microbubble characteristic as appropriate to the requirementsof given applications. In a variety of embodiments, the user can inputwhich microbubbles are being administered. Although several methods fornormalizing microbubble harmonic amplitudes have been described above,one of ordinary skill in the art would recognize that there are numerousways to normalize microbubble harmonic amplitudes in accordance with therequirements of given applications.

Localizing Brain Injury

In order to classify a left and right hemisphere, knowing the totalwidth of the brain can be useful. Head size can be calculated by theportable ultrasound device. In a variety of embodiments, a firsttransducer assembly can send a test ping across the patient's skull.Based on the time the test ping was received by the second transducerassembly placed on the opposite side of the skull, the distance betweenthe transducer assemblies can be calculated. The distance between thetransducer assemblies can provide an estimate of the size of thepatient's skull. In some embodiments, a single transducer assembly cansend a test ping using a transmit element across the patient's skull andmeasure the time for the reflection of the ping to be picked up by thereceive element of the single transducer assembly. The time between thetransmission of the test ping and receiving the reflection of the testping can allow the portable ultrasound device to calculate the size ofthe patient's skull.

In many embodiments, a portable ultrasound device can discern betweenthe right and left hemispheres of a brain based on the travel time ofultrasound signals. In some embodiments, hemisphere responses can beassigned based on the determination of a center line. The center linecan be determined as the point at which a signal from one transducerassembly has traveled half the distance to a contralateral transducerassembly. In numerous embodiments, a sawtooth wave, or any other wavewith a smooth ramp can be used to discern the right and lefthemispheres. Waves with smooth ramps and defined peaks can allow foraccurate measurements of propagation time (e.g. time from transmissionof a signal peak to a peak detection at a receiver).

In a variety of embodiments, the peak amplitude focal distance of thetransmit element of a transducer assembly can be used to distinguishbetween signals from the different hemispheres. In many embodiments, theportable ultrasound device smoothly ramps up the peak voltage andmonitors for the first indication of microbubble signals. The firstoccurrence of microbubble signals is located approximately at the focaldistance of the transducer assembly. In a variety of embodiments, thefocal distance is approximately 40 mm. However, the focal distance of atransducer assembly can be modified to be any distance from the face ofthe transducer assembly. At the focal length of the transducer assembly,the beam of ultrasound will be at a higher intensity. The tolerancearound the distance measurement can be a function of how “sharp” theshape of the peak is at the focal distance, how repeatable the voltagethreshold is for microbubble excitation, and/or how repeatable the focaldistance is from transducer assembly to transducer assembly. In thisway, portable ultrasound devices can discern between the left and righthemisphere.

In many embodiments, precise measurement of the time for signals tobreach the center line of the patient's head in ipsilateralconfiguration is determined by transmitting ultrasound across the head.The portable ultrasound device can calculate head symmetry based on thetravel time of the ultrasound pulse across the head. In numerousembodiments, the travel time of the ultrasound pulse across the head isidentical to the round-trip travel time to the centerline for theipsilateral approach. In a variety of embodiments, the measurements canbe taken in the presence of microbubbles which allows the portableultrasound device to calculate the time necessary for microbubbleexcitation and algorithmic detection.

Further, subharmonic microbubble responses and/or superharmonicmicrobubble responses can be used to localize brain injury. Thedifference in harmonics across hemispheres can be utilized to estimateintracranial pressure. In numerous embodiments, superharmonics and/orsubharmonics can be normalized based on received normal harmonicresponses.

While specific methods of discerning hemispheres have been describedabove, any number of methods can be used to assign a left and righthemisphere using a portable ultrasound device in accordance with therequirements of given applications. By determining left and righthemispheres, brain injuries can be localized to a specific side of thebrain. However, to further localize brain injuries, precision spatialsegmentation can be performed. Methods for performing precision spatialsegmentation are discussed below.

Performing Precision Spatial Segmentation

Portable ultrasound devices can apply precision spatial segmentation tothe threshold comparisons. The frequency of return signals using aportable ultrasound device can have a spatial resolution on the order of1 mm. Frequencies on this order can allow for segmentation of eachhemisphere of the brain into subregions, and each subregion can becompared to its mirror subregion in the opposite hemisphere. In manyembodiments, a suggested diagnosis can be determined for each subregion.In this way, localized injuries such as blockages or bleeds of smallarteries can be detected. Further, because middle cerebral artery (MCA)blockages impact nearly the entire hemisphere, and other afflictionssuch as bleed or blockage of smaller arteries have a degree oflocalization, MCA blockage can be determined at the exclusion of bleedand/or blockage of a smaller artery.

In numerous embodiments, precision spatial segmentation can be performedusing a synchronized transmit/receive method. In order to calculatewhere in the tissue a return signal originates from, the travel time ofthe signal can be used. The more precisely the travel time can bedetermined, the more precisely the location of the signal can becalculated. Precision and/or accuracy of measurements such as traveltime can be achieved using calibration processes and self-check tests.Processes for improving precision and/or accuracy are discussed furtherbelow.

In order to measure the travel time, various methods can be used. Inmany embodiments, the method includes recording an accurate timestampwhen the start of transmission of ultrasound occurs, and recordingaccurate timestamps in conjunction with each data point recorded for thereturn signal. In a variety of embodiments, the method includescapturing the transmitted signal in the same data acquisition channelthat has an “enable” line for the start of data acquisition. The controlline that is used to start the transmission can be connected to theenable line of the start of data acquisition. In numerous embodiments,at least the first data sample will still not have a voltage consistentwith a received signal, but when the receive signal is acquired and isdetected, the time between the start of the received signal and thefirst data point (at the start of transmission) can be accuratelycalculated.

In many embodiments, calculated travel time is used to time-box thereceived signal into slices. Slices are portions of the signal thatcorrespond to the harmonic responses between two points in the brain.Slices can describe harmonic responses of any region from the spatialresolution of the transducer assembly to the size of the brain. In manyembodiments, slices are standardized to 1 cm. However, in numerousembodiments, while the first slice (i.e. from the face of the transducerassembly to 1 cm away) is 1 cm, each subsequent slice may be 1 cm largerin such a way that the start point is always the face of the transducerassembly. In this way, slices of increasing size can be analyzed untilan abnormality is detected, and the last centimeter added can be assumedto be the location of the injury within the brain. Further, in a varietyof embodiments, each slice can be masked by the previous slice in orderto observe only the harmonic responses present at that location.

While several methods for precision spatial segmentation have beendescribed above, one of skill in the art would appreciate that there area variety of ways to perform precision spatial segmentation using aportable ultrasound device in accordance with the requirements of givenembodiments. Further, while several methods of generating diagnosticsupport data have been described above, the diagnostic tests that thediagnostic support data can be based on are numerous. Processes forperforming many diagnostic tests using a portable ultrasound device aredescribed below.

Performing Diagnostic Tests Using Portable Ultrasound Devices

Portable ultrasound devices in accordance with many embodiments of theinvention can be used to perform diagnostic tests on patients. In manycases, it is difficult to detect and classify strokes, and to localizethe stroke event to a particular area of the brain. It is common formedical professionals to use magnetic resonance imaging (MRI) or anx-ray computed tomography (CT) scan to detect and localize strokes.Portable ultrasound devices can use microbubbles as an acoustic markersto track blood flow in conjunction with at least one transducer assemblyto effectively detect, classify, and localize strokes in a patient.

Turning now to FIG. 9 , a method for performing a diagnostic test on apatient using a portable ultrasound device is illustrated in accordancewith an embodiment of the invention. Process 900 includes calculating(910) test parameters based on the patient's biometrics. Biometrics caninclude, but are not limited to, head size, cranial thickness, headshape, brain shape, baseline acoustic measurements, and/or any otherbiometric measurement as appropriate to requirements of givenapplications. Once test parameters have been established, transmissionof ultrasound pulses from one of the transducer assemblies can begin(920). In many embodiments, one transducer assembly transmits, and onereceives. In many embodiments, one transducer assembly transmits, andboth receive. In numerous embodiments, both transducer assembliestransmit, and both or one transducer assembly receives. In variousembodiments, the portable ultrasound device alternates which transducerassembly transmits.

Microbubbles can be administered (930) to the patient, and contra sideharmonic amplitudes can be monitored (940). In this way, the portableultrasound device can have backup readings. However, monitoring contraside harmonic amplitudes is not required. The portable ultrasound devicecan calculate (950) latency to set the listening time. In manyembodiments, a test ping can be sent from at least one transducerassembly. A second transducer assembly on the opposite side of the skullcan pick up the ping, and the travel time can be recorded. In manyembodiments, the transducer assembly that sent the test ping can receivethe reflection of the test ping from the opposite side of the skull,which can be used to calculate latency. Further, a test pulse can betransmitted between two contralateral transducer assemblies whilemicrobubbles are in the patient. The difference in the transmit time ofa baseline test pulse without microbubbles and the transmit time at thesame frequency with microbubbles can indicate the microbubble latency.As one can appreciate, there are numerous ways to calculate latencydepending on the number of transducer assemblies used as appropriate tothe requirements of a given application. The portable ultrasound devicecan continue transmitting (960) ultrasound pulses with right/leftinterleaving, while monitoring (970) ipsilateral side harmonicamplitudes and delays. Monitored ipsilateral side harmonic amplitudesand delays can be used by portable ultrasound devices to distinguishmicrobubble harmonic response patterns in order to generate diagnosticsupport data using methods described above. Recorded data can be storedby the portable ultrasound device on a machine readable medium such asrandom access memory, a hard disk drive, a solid state drive, a flashdrive, or any other form of machine readable medium. Ultrasound pulsescan be transmitted over a range of voltages and/or frequencies. Theportable ultrasound device can detect (990) wash-out of microbubbles bydetermining that signal levels have receded. In many embodiments,diagnostic tests performed by the portable ultrasound device are on apredetermined timer. If the timer hits a predetermined amount of time,the test will terminate.

While a specific method for performing a diagnostic test on a patientusing a portable ultrasound device is discussed above with respect toFIG. 9 , there are numerous approaches to performing a diagnostic testin accordance with the requirements of a given application. In manyembodiments, diagnostic tests can be performed using a contralateralreceiving approach. In numerous embodiments, diagnostic tests can beperformed using an ipsilateral receiving approach. Methods forperforming diagnostic tests using contralateral and ipsilateralreceiving approaches are described below.

Contralateral Receiving Approach

Contralateral receiving approaches involves transmitting ultrasoundusing a first transducer assembly and receiving the ultrasound using asecond transducer assembly on the opposite side of the head from thefirst transducer assembly (the “contra” position). Turning now to FIG.12 , a conceptual diagram illustrating a contralateral receivingapproach in accordance with an embodiment of the invention isillustrated. A process for performing a contralateral receiving approachis illustrated in FIG. 13 .

Process 1300 includes calculating (1310) test parameters based onpatient biometrics. In many embodiments, calculating test parameters isperformed using methods described below. Process 1300 also includescontinuously transmitting (1320) ultrasound from a transmittingtransducer assembly. Microbubbles can be administered (1330) usingmethods similar to those described above. In many embodiments,microbubbles are administrated prior to beginning continuous ultrasoundtransmission. Contra side harmonic amplitudes can be monitored (1340)using the receiving transducer assembly. If the diagnostic test has notbeen finished, the transmitting and receiving transducer assemblies canswitch (1350) roles. That is, the transmitting transducer assembly canbecome the receiving transducer assembly and vice versa. If the test iscompleted, the process can be terminated. In numerous embodiments, steps1510-1540 can be repeated multiple times prior to switching thetransducer assemblies. The contralateral receiving approach uses atleast two transducer assemblies at the same time. However, theipsilateral receiving approach can be performed using a singletransducer assembly. A discussion of an ipsilateral receiving approachcan be found below.

Ipsilateral Receiving Approach

The ipsilateral receiving approach involves using a transducer assemblyto both transmit and receive ultrasound signals. As discussed above,signals received can be time-boxed in order to better isolate harmonicsgenerated in the hemisphere of the brain closest to the ultrasoundtransceiver. A conceptual diagram illustrating a contralateral receivingapproach in accordance with an embodiment of the invention isillustrated in FIG. 14 .

Turning now to FIG. 15 , a process for performing an ipsilateralreceiving approach is illustrated in accordance with an embodiment ofthe invention. Process 1500 includes calculating (1510) test parametersbased on patient biometrics. In many embodiments, calculating testparameters is performed using methods described below. Process 1500 alsoincludes continuously transmitting (1520) ultrasound from a transducerassembly. Microbubbles can be administered (1530) using methods similarto those described above. In many embodiments, microbubbles areadministrated prior to beginning continuous ultrasound transmission.Ipsi-side harmonic amplitudes can be monitored (1540) using thetransducer assembly used for transmitting. If the diagnostic test hasnot been finished, a second transducer assembly placed on the oppositeside of the patient's head can be used to measure the oppositehemisphere of the brain. If the test is completed, the process can beterminated.

While processes for performing diagnostic tests in accordance with anembodiment of the invention is described above, a person of ordinaryskill in the art would recognize that there are any number of ways thatportable ultrasound devices can perform diagnostic tests in accordancewith the requirements of given applications. Different processes couldinclude, but are not limited to, using different test parameters, usingdifferent ordering and/or number of tests, using different tests, and/orusing different numbers of transducer assemblies. Diagnostic tests canbe tailored to specific patients and/or specific scenarios using testparameters. Methods for generating test parameters are described below.

Generating Test Parameters Using Portable Ultrasound Devices

Prior to performing diagnostic tests using a portable ultrasound device,test parameters can be determined to direct the test. Proper calculationof test parameters can enable more accurate results and diagnoses. Innumerous embodiments, test parameters are determined using calibrationtests. In many embodiments, a test-pad can be included on the portableultrasound device. The test-pad can be used during self-checks andself-validation to provide a standardized testing environment. Users canbe prompted to hold at least one transducer assembly against thetest-pad. In many embodiments, the test pad has a holder for at leastone transducer assembly to further standardize the testing environment.The test-pad can include a variety of sensors, or cover a variety ofsensors used to perform self-checks. In numerous embodiments,self-checks occur in the air, on the patient, or using a differentmedium as appropriate to the requirements of given applications.

Turning now to FIG. 10 , a process for calculating various testparameters using a portable ultrasound device in accordance with anembodiment of the invention is illustrated. Process 1000 includeschecking (1010) for proper head contact between at least one transducerassembly and the patient's head, and checking (1020) the alignment ofthe at least one transducer assembly. Head size can be calculated(1030), and left vs. right path quality can be determined (1040).Transmission power level can be chosen (1050). In many embodiments, aseries of at least one test ping at multiple, predetermined power levelscan be transmitted in order to choose the power level at which signalclarity is best. Portable ultrasound devices can calculate (1060)baseline (tissue) harmonic amplitudes. The processes for determiningtest parameters referenced in FIG. 10 are described in further detailbelow, however, any number of specific steps can be used to determinetest parameters in accordance with given applications

Confirming Transducer Assembly Alignment

In many embodiments, there are two transducer assemblies that are placedin proper contact with the patient's head. In numerous embodiments, thetransducer assemblies are placed on opposite sides of the patient's headabove the ears over the temporal bone in a contralateral fashion. In avariety of embodiments, the portable ultrasound device detects whetherthe transducer assembly is in contact with the body by monitoringimpedance. Impedance monitoring can occur periodically to confirm thatthere is no loss of contact during operation of the portable ultrasounddevice.

The alignment of the transducer assemblies can be checked. Alignment canbe checked by transmitting test pings across the patient's skull.Depending on how the ultrasound test pings are received, the portableultrasound device can determine whether or not the transducer assembliesare properly placed. In many embodiments, the portable ultrasound devicecan detect whether a transducer assembly is placed properly and whetherskull thickness is acceptable by monitoring signal level received by acontralateral transducer assembly. In a variety of embodiments, propertransducer assembly placement and acceptable skull thickness aredetected using a single transducer assembly on one side of the skull bytransmitting a signal and monitoring for the return signal after aprescribed time delay. This can indicate that the signal has propagatedpast the skull, into the brain tissue, and returned through the skullagain. In numerous embodiments, the degree of signal symmetry between aleft transducer assembly and right transducer assembly can be monitoredto determine proper contact and/or placement of the transducerassemblies. If the tissue and/or microbubble resonance peaks are in thesame locations between a left to right and right to left signaltransmission, it is likely that the transducer assemblies are placedsymmetrically. In some embodiments, only signals with frequencies thatare known to not be affected by microbubbles are checked.

Alignment can also be checked by comparing right/left signal traveltimes. A first transducer assembly can transmit while a secondtransducer assembly receives. Appropriate time-boxing can be done tohelp ensure that there are no echoes being considered. After the directtransmission traveling once across the head has been measured, then thesecond transducer assembly transmits and the first transducer assemblyreceives. The travel time should be the same assuming only one directpath across. If one transmission took less time than the other, then itcan suggest that the longer time involved echoes rather than a directpath which would occur due to a lack of alignment. Correction of thealignment can be indicated until the travel times are essentially thesame. Once travel times are the same, then signal strengths can becompared. Since each signal is traveling the same path, the signalstrengths should be effectively identical assuming similar transducerassembly performance and assuming co-axial alignment. Assuming that thetransducer assemblies are verified to be working properly and calibratedto be performing as expected, then the primary contributor to signaldifference can be assumed to be lack of alignment. If the signalreceived by one transducer assembly is lower than the other, then theopposite transducer assembly might not be pointed co-axially. However,there are a variety of ways that alignment can be determined, including,but not limited to, those described above, manual checks, positioningbands, or any other alignment method as appropriate to the requirementsof a given application.

The user of the portable ultrasound device can be alerted that thetransducer assemblies are properly and/or improperly placed via anauditory and/or visual cue. In numerous embodiments, audio feedback innear real-time can be generated in order to help the user to place thetransducer assemblies. Iterative measurements can be taken bytransmitting a positioning test ultrasound signal and listening to theecho return can be performed similar to a path quality measurement checkin such a way that an audio output speaker is configured to emit a soundwith pitch proportional to the returned signal amplitude so that theuser can locate the optimum placement of the transducer assemblies. Inmany embodiments, optimum placement is determined by measuring theamount of signal received form a test pulse. Amount of signal can bemeasured by comparing the voltage used to generate the test pulse withthe voltage received from the test pulse, measuring the amplitude of thesignal received compared to the signal transmitted, calculating acousticpressure, or any other measurement as appropriate to the requirements ofa given application. In numerous embodiments, a visual feedback is givento the user in order to assist with finding optimal placement of thetransducer assemblies. Portable ultrasound devices can use a signallevel indicator on a display in order to give visual feedback. However,any number of visual and/or audio feedback methods can be used in orderto assist the user with proper transducer assembly placement. In manyembodiments, the positioning signal is transmitted at 220 kHz. In otherembodiments, any of a variety of signals and/or frequencies can beutilized as appropriate to the requirements of a given application.Alignment checks can be performed a single time, or multiple timesduring the use of a portable ultrasound device on a patient in order toconfirm that there is no loss of proper placement during operation.

Checking Path Quality

Portable ultrasound devices can check path quality in any of a varietyof ways. Checking path quality can verify accurate data recording duringtests performed by portable ultrasound devices. Portable ultrasounddevices can check path quality prior to performing diagnostic tests. Inmany embodiments, portable ultrasound devices periodically check pathquality. In numerous embodiments, portable ultrasound devicescontinuously check path quality.

Portable ultrasound devices can initiate at least one test ping fromeach of a left transducer assembly and a right transducer assembly.Based on the quality of the reception of each signal, signal quality canbe determined using a left transducer assembly to transmit and using aright transducer assembly to transmit. A check of path quality can besimilar to a check of alignment as described above. In many embodiments,path quality is measured based upon tissue noise signals that aredetected during a baseline test. Tissue can create scattered signalseven without the presence of microbubbles. Accordingly, significantharmonics in the absence of microbubbles can indicate poor path quality.The scattered tissue signals are omnidirectional and return to theipsilateral transducer assembly without any reflection path.

During the transmission of ultrasound pulses, the portable ultrasounddevice can periodically recheck the head contact path quality in orderto maintain acceptable performance. Ipsilateral path quality can beassessed by transmitting, then waiting for the transmitted echo toreturn, thereby measuring the audio transmission path quality on around-trip basis. By assessing path quality on both sides of the head inadvance of measurements, microbubble signals can be normalized forcomparison between the two sides. Path quality assessment can allow thedetection of unusual conditions such as a person with a plate in his orher head, abnormal brain morphologies, severe head injuries resulting indamage to the skull on one side, or any other unusual condition asappropriate to the requirements of given applications. Skullabnormalities can be characterized by a fairly predictable signalreflection occurring approximately 1 cm from the face of the transducerassembly. 1 cm from the face of the transducer assembly can be assumedto be the flesh/bone transition layer, however this distance can bevariable based on the type of transducer assembly used, the patient'sskin, the ultrasound gel pad used, or any number of other differences inconstruction as appropriate to the requirements of given applications.The portable ultrasound device can configure the transducer assembly toadapt to the abnormal morphology.

In many embodiments, the portable ultrasound device can detect a changein impedance of the transducer assembly circuit by monitoring the“ring-up” profile of the transducer assembly. The portable ultrasounddevice can configure a transducer assembly to produce a signal of apredetermined amplitude, which has a repeatable ring-up signature thatis a function of its impedance and the circuit driving it. The ring-uppattern can be measured and modifications from the expected pattern canbe measured. Deviations from the expected pattern can be caused by themedia between the transmission element and the receiving element. Inthis way, changes of impedance can be measured. A large change inimpedance can signify that there is a short to ground through thepatient's body. In a variety of embodiments, the portable ultrasounddevice has a library of ring-up patterns that can be associated withvarious conditions.

While several methods of checking for path quality have been describedabove, portable ultrasound devices are not limited to using thesemethods. Methods for determining path quality can take on any of anumber of forms as appropriate to the requirements of specificembodiments. In addition to the tests described above, portableultrasound devices can perform additional self-check tests to furthercalibrate the device, and confirm proper working order of the device.Methods for performing self-check tests are described below.

Methods for Performing Self-Check Tests Using a Portable UltrasoundDevice

Self-check tests can be performed by portable ultrasound devices inaccordance with various embodiments of the invention. Self-check testscan confirm that the portable ultrasound device is functional and readyto perform diagnostic tests on a patient. Self-check tests can calibratea portable ultrasound device to verify that all components areconfigured to record and transmit reliable information. Self-check testscan be performed in a variety of ways and in a variety of orders.

A process for performing self-checks using a portable ultrasound devicein accordance with an embodiment of the invention is illustrated in FIG.8 . Process 800 includes confirming (810) whether the transducerassemblies are properly positioned on the patient. In many embodiments,checking (810) that the transducer assemblies are not on the patient isdone by sending safe test pings from at least one transducer assembly.In numerous embodiments, checking (810) is done manually by a user.While manual checks can be performed, automatic failsafe checks can beperformed as well.

Process 800 can include performing (820) system and functional tests. Inmany embodiments, system and functional tests involve confirming thatthe transducer assemblies are capable of sending and receivingultrasound. The portable ultrasound device can also check for properconnections between components to validate that all transducer assemblyelements are functioning properly. The portable ultrasound device canalso check (830) for transmit/receive (TX/RX) reversal in order todetermine electrical assurance. By measuring the transmit voltageachieved at a certain power setting at a transmit element and checkingthe voltage level obtained at a receive element, the portable ultrasounddevice can determine if TX/RX reversal may have occurred in eithertransducer assembly. In many embodiments, TX/RX reversal can be detectedby characterizing impedance and/or returned signal signature that occursin free air when reversal occurs. Reversal can also be detected bycalculating impedance based on values returned by digital potentiometerselectrically coupled to the ultrasound transducer assemblies. In severalembodiments, the portable ultrasound device checks (840) the relay quiettime delay and checks (850) the noise level. In many embodiments, thenoise level can be monitored before and after signal generation andmeasurements to verify that noise levels are not excessively riskingimproper signal analysis. In some embodiments, the portable ultrasounddevice uses the results of the noise level checks to estimate the noisepower. The output voltage can be calibrated (860) and the transducerassemblies can be calibrated (870). Methods for calibrating transducerassemblies are described below.

Transducer Assembly Integrity and Calibration Tests

In addition to the tests above, portable ultrasound devices can performsystem and functional tests can include a variety of calibration testsand integrity checks that can determine whether or not the portableultrasound device is in working order. Such tests can include, but arenot limited to, circuit integrity tests, transducer assembly performancetests, or any other functional test as appropriate to the requirementsof given applications.

In many embodiments, short circuit detection is performed. Portableultrasound devices in accordance with a number of embodiments of theinvention can monitor the current output to at least one transducerassembly, and monitor the current returned from the at least onetransducer assembly, and turn off the circuit if the current returned issignificantly less than the output current as indicative of a shortcircuit. Further, portable ultrasound devices can determine if there isa fault through the patient based on human impedance. Given that theaverage range of impedance for a human body has been determined, ifthere is more electrical load than the transducer applies, but notenough to be caused by a short circuit, then there may be a faultthrough the body. In the event that there is a short circuit or a fault,portable ultrasound devices can automatically shut down.

In many embodiments, functional tests of the transducer assembliesinclude making sure that the receive elements are properly functioning.In some embodiments, there is cross-talk between transducer assembliesin free air, which can be used to verify functionality. Minimal signalis expected to be detected on the receive chain during a free airtransmit check. The targets for isolation that can be achieved intransducer assemblies can be on the order of 50 dB and receive chainfiltering of a 220 kHz signal can add approximately an additional 50 dBof suppression. In order to perform the functional test, a transmitterelement can be switched so it is connected to the receiver. The receivercan be at the junction of the receiver and the first high pass filter inthe receive chain, and a characterization of the impedance at thisconnection point can be obtained. Once the characterization of theimpedance is obtained, it can be calculated what voltage should beobserved when the transmitter attempts to transmit a specified signal atthis junction. The voltage obtained can be much lower than that of thetransmit element, and can be predictable in order to achieve validationof functionality. Difference in receiver element impedance can becalculated and signal measurement normalization factors can becalculated.

Part to part variations in components can affect measurements taken byultrasound devices. Component behaviors can be characterized andcompiled into profiles. Each component can have an individual profile.Profiles can be stored in the memory of portable ultrasound devices.Profiles can be used in calibration to tune measurement processes. Insome embodiments, portable ultrasound devices have a non-volatile memorydevice used to store profiles. In a variety of embodiments, portableultrasound devices can automatically detect which profiles should beused based on the attached components. Automatic detection can occurthrough an exchange of information between components. Automaticdetection can occur based on unique resistor values in connectioncables. In some embodiments, serial numbers can be used to accessappropriate profiles. In numerous embodiments, profiles can be storedremotely and accessed via a network connection.

In many embodiments, portable ultrasound devices can conduct variouscalibration steps on the transducer. Portable ultrasound devices candetect when gel pads have been connected based on change in electricalload in the transducer. Further, in many embodiments, confirmation thatthe gel pads have been connected can be achieved by identifying a changein impedance on one transducer assembly, a lack of path quality betweenthe two transducer assemblies, and then a subsequent similar change inimpedance of the other transducer assembly. The amplifier section ofeach transducer assembly that drives the transmission of the transducerassembly can be calibrated in such a way that the desired acousticoutput is nearly identical for both sides at each target power level.The portable ultrasound device can measure the output voltage obtainedat one or more settings of the transmit circuit, and then determine theoptimum voltage setting for each power level such that the two sideshave equal output power given the individual impedance of the transducerassemblies. In many embodiments, the portable ultrasound device capturesat least one measurement of the signals received by the receive elementswhile performing the calibrations and/or by the opposite transmitelement (if they are in contact with a common media) in order to providemeasurements of the overall conversion efficiency for both transducerassemblies, through the transmit element(s) and back through the receiveelement(s). The received calibration signals can be used to tune thecalibration of the transmitter settings, and/or the relative performanceof each side.

In a variety of embodiments, a closed-loop test is done where atransmitter element of a transducer assembly is driven and the receiverelement is monitored. A connection before the high pass filter of thereceive chain to the analog to digital converter can be made so that thesignal can be detected prior to the filters. In this way, thecalibration of the transducer assemblies can be automated by theportable ultrasound device.

In a number of embodiments, the calibration process includes a firsttransmit element producing at least one reference burst at a selectedtransmit output voltage. Each receive element can receive thetransmission from the transmit element. Next, the opposite transmitelement produces the same reference burst or bursts and each receiveelement can receive the second set of reference bursts. For eachmeasurement sequence, the peak amplitude can be calculated. Thetransducer assemblies can be analyzed using the calculated peakamplitudes and a matrix of preset reference values. In otherembodiments, calibration can be performed using any of a variety ofwaveforms and signal processing techniques.

In certain embodiments, calibration includes latency detection. Latencycan be measured in a variety of ways. In some embodiments, there issignificant part to part variation in transmit latency and/or latency ofdrug to drug variation in latency of microbubbles. A test ping can betransmitted from one transducer assembly to a second transducer assemblyand the time for the signal to travel between the two transducerassemblies can be factored out. The remaining time can indicate thelatency due to part to part variation.

In many embodiments, a target amplitude for the transducer assemblies ischosen. The target amplitude can be a preconfigured target amplitude, ora user input target amplitude. The portable ultrasound device can theninitiate test transmission of ultrasound at the target amplitude using atransmit element, and monitor the actual amplitude obtained at a receiveelement. An adjustment factor can be calculated to apply subsequentsettings so that the actual amplitude will conform to the testparameters. In a variety of embodiments, one or more digitalpotentiometers can be electrically coupled to the ultrasound transducerassemblies. The digital potentiometers can be used to tune theultrasound transducer assemblies to standardize the output level. Inthis way, self-calibration can allow the portable ultrasound device tocompensate for many part-to-part variations and mismatches that arelikely to occur throughout the circuitry.

In numerous embodiments, for a period after the transducer assemblieshave been set on a patient's head, the acoustic properties of the gelpads can shift. Shifts in the acoustic properties can be caused by achange in temperature as they reach equilibrium with their newenvironment including the patient's head. Shifts in acoustic propertiescan also be caused by changes in pressure as they settle. The perioduntil the acoustic properties stop changing enough to significantlyimpact data collection is called the “stabilization period.” In manyembodiments, portable ultrasound devices can calculate stabilizationperiods. Calculating stabilization periods can involve monitoringharmonic responses and measuring how they change over time. In a varietyof embodiments, once stability is achieved, diagnostic testing canproceed.

When ultrasound signals are transmitted, there can be a reflection ofthe original transmission from the skull boundary, as well as unwantedharmonic reflections. Skull boundary reflections can be triggered whenthere is a large change in velocity as the ultrasound waves enter theskull. Unwanted harmonics can include harmonics that are not relevant tothe current testing. For example, under conditions where the transmitfrequency is 220 kHz, harmonics of interest may only be 880 kHz, 1,100kHz, and 1,320 kHz. Other full harmonics and/or half harmonics not ofinterest can be considered noise. In many embodiments, by measuring thereflected transmission from the skull boundary, the response can be usedas a proxy for knowing the amplitude and/or phase angle of unwantedharmonic reflections. Portable ultrasound devices can use the reflectedtransmission to screen out noise using measured parameters duringdiagnostic testing.

In numerous embodiments, portable ultrasound devices can determinewhether or not components or circuitry has been manipulated, tamperedwith, or serviced. Portable ultrasound devices can include a systemclock chip, and a backup clock chip with a separate power source. Thepower supply for the backup clock chip can be connected to the openingin the casing of the portable ultrasound device such that electricalflow is halted if the casing is opened. In numerous embodiments, thebackup clock chip cannot be accessed without breaking the casing of theportable ultrasound device. When the system is powered on, if there is adiscrepancy between the system clock time and the backup clock time,there is an indication that the unit has been manipulated. If there isan indication that the unit has been manipulated, the portableultrasound device can initiate calibration tests and/or require anauthorization code and/or maintenance information to function. Thebackup clock chip can be resynced to the system clock afterauthorization has been established.

As one can readily appreciate, a variety of calibration tests and checkscan be performed to confirm that the portable ultrasound device isworking properly. The ordering of the steps can be modified, and stepscan be omitted and/or added as appropriate to the requirements of givenapplications. Accuracy and precision of measurements taken usingportable ultrasound devices can be increased by performing self-checktests to confirm functionality of components, and calibration tests todetect variance in the testing scenario.

Post Natal Brain Damage Diagnosis

In numerous embodiments, portable ultrasound device can be used todetect postnatal brain damage. In many cases, there is no easy way totest whether an infant might suffer from severe brain damage such asintracranial hemorrhage, stroke, intracranial hypertension caused by atumor, or any other severe brain injury. A transducer assembly can beattached to the infant's head. In many embodiments, the transducerassembly is attached to the anterior fontanelle. The transducer assemblycan collect tissue harmonic frequency responses. If there is elevatedintracranial pressure, the signal amplitudes can be decreased comparedto normal pressure responses. Normal pressure responses can bepredetermined and stored in the memory of a portable ultrasound deviceand/or a server system. Normal pressure responses can be calculatedusing any of, but not limited to, pulse measurements, blood pressuremeasurements, temperature, weight, and any other metric as appropriateto the requirements of a given application.

Although the present invention has been described in certain specificaspects, many additional modifications and variations would be apparentto those skilled in the art. In particular, any of the various processesdescribed above can be performed in alternative sequences in order toachieve similar results in a manner that is more appropriate to therequirements of a specific application. It is therefore to be understoodthat the present invention can be practiced otherwise than specificallydescribed without departing from the scope and spirit of the presentinvention. Thus, embodiments of the present invention should beconsidered in all respects as illustrative and not restrictive.

What is claimed is:
 1. A system for measuring intracranial pressure,comprising: a processor; a headband comprising a first ultrasoundtransmitter and a first ultrasound receiver, where the first ultrasoundtransmitter is positioned to transmit ultrasound in the direction of thefirst ultrasound receiver; and a memory, the memory containing anapplication that configures the processor to: receive a mean arterialpressure measurement of a patient; transmit a first ultrasound signalfrom the first ultrasound transmitter laterally across a brain of apatient; receive a first recorded ultrasound signal corresponding to thefirst ultrasound signal using the first ultrasound receiver, where thefirst recorded ultrasound signal comprises a first set of harmonicresponses generated by microbubbles present in blood in the brain of thepatient in response to the first ultrasound signal; approximate a meantransit time for the microbubbles to pass through the brain based on theharmonic responses; estimate a cerebral perfusion pressure based on themean transit time; and calculate an intracranial pressure of the brainas the difference between the mean arterial pressure of the patient andthe estimated cerebral perfusion pressure.
 2. The system of claim 1,wherein to estimate the cerebral perfusion pressure based on the meantransit time, the application further configures the processor tocalculate a half peak full width parameter correlated to the meantransit time.
 3. The system of claim 1, wherein cerebral perfusionpressure is inversely correlated with the mean transit time.
 4. Thesystem of claim 1, wherein the application further directs the processorto identify a brain bleed based on the intracranial pressure.
 5. Thesystem of claim 4, wherein the application further directs the processorto time-box the first set of harmonic responses in order to locate thebrain bleed within the brain.
 6. The system of claim 4, wherein theapplication further directs the processor to identify whether the brainbleed is a hemorrhagic or an ischemic stroke.
 7. The system of claim 1,wherein the headband further comprises a second ultrasound transmitterand a second ultrasound receiver; where the second ultrasoundtransmitter is positioned to transmit ultrasound in the direction of thesecond ultrasound receiver; where the first ultrasound transmitter andthe second ultrasound receiver are positioned by the headband over afirst temple of the patient's head; where the second ultrasoundtransmitter and the first ultrasound receiver are positioned by theheadband over a second temple of the patient's head; and where theapplication further directs the processor to approximate the meantransit time for the microbubbles to pass through the brain based on asecond set of harmonic responses generated by the microbubbles inresponse to a second ultrasound signal transmitted by the secondultrasound transmitter.
 8. The system of claim 7, wherein the firstultrasound transmitter and the second ultrasound receiver are a singlefirst ultrasound transducer; and the second ultrasound transmitter andthe first ultrasound receiver are a single second ultrasound transducer.9. The system of claim 5, wherein the first ultrasound transmitter andthe second ultrasound receiver are a single first ultrasound transducer;and the second ultrasound transmitter and the first ultrasound receiverare a single second ultrasound transducer.
 10. The system of claim 1,wherein the mean arterial pressure measurement of a patient is obtainedusing a blood pressure cuff.
 11. A method for measuring intracranialpressure, comprising: receiving a mean arterial pressure of a patient;transmitting a first ultrasound signal from a first ultrasoundtransmitter laterally across a brain of the patient to a firstultrasound receiver; receiving a first recorded ultrasound signalcorresponding to the first ultrasound signal using the first ultrasoundreceiver, where the first recorded ultrasound signal comprises a firstset of harmonic responses generated by microbubbles present in blood inthe brain of the patient in response to the first ultrasound signal;approximating a mean transit time for the microbubbles to pass throughthe brain based additionally on the first set of harmonic responses,using a processor; estimating a cerebral perfusion pressure based on themean transit time, using the processor; and calculating an intracranialpressure of the brain as the difference between the mean arterialpressure of the patient and the estimated cerebral perfusion pressure,using the processor.
 12. The method of claim 11, wherein estimating thecerebral perfusion pressure based on the mean transit time comprisescalculating a half peak full width parameter correlated to the meantransit time.
 13. The method of claim 11, wherein cerebral perfusionpressure is inversely correlated with the mean transit time.
 14. Themethod of claim 11, further comprising identifying a brain bleed basedon the intracranial pressure.
 15. The method of claim 14, furthercomprising time-boxing the harmonic responses in order to locate thebrain bleed within the brain.
 16. The method of claim 14, furthercomprising identifying whether the brain bleed is a hemorrhagic or anischemic stroke.
 17. The method of claim 11, further comprisingtransmitting a second ultrasound signal from a second ultrasoundtransmitter laterally across the brain to a second ultrasound receiver;receiving a second recorded ultrasound signal corresponding to thesecond ultrasound signal using the second ultrasound receiver, where thesecond recorded ultrasound signal comprises a second set of harmonicresponses generated by microbubbles in response to the second ultrasoundsignal; and approximating the mean transit time for the microbubbles topass through the brain based additionally on the second set of harmonicresponses.
 18. The method of claim 11, wherein the mean arterialpressure measurement of a patient is obtained using a blood pressurecuff.